HereditasVolume 39, Issue 3-4 p. 493-504 Open Access IRRADIATION EFFECTS, SEED SOAKING AND OXYGEN PRESSURE IN BARLEY L. EHRENBERG, L. EHRENBERG STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorA. GUSTAFSSON, A. GUSTAFSSON STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorU. LUNDQVIST, U. LUNDQVIST STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorN. NYBOM, N. NYBOM STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this author L. EHRENBERG, L. EHRENBERG STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorA. GUSTAFSSON, A. GUSTAFSSON STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorU. LUNDQVIST, U. LUNDQVIST STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this authorN. NYBOM, N. NYBOM STOCKHOLM AND SVALÖF, SWEDENSearch for more papers by this author First published: August 1953 https://doi.org/10.1111/j.1601-5223.1953.tb03433.xCitations: 7AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL LITERATURE CITED 1 Alexander, P. and Fox, M. 1952. Mode of action of agents giving protection from radiation. Nature 170: 1022– 1023. 2 Allen, A. O. 1948. Radiation chemistry of aqueous solutions. Journ. Phys. and Colloid Chem. 52: 479– 490. 3 Anderson, E. H. 1951. The effect of oxygen on mutation induction by X-rays. Proc. Nat. Acad. Sci. 37: 340– 349. 4 Baker, W. K. and Edington, C. W. 1952. The induction of translocations and recessive lethals in Drosophila under various oxygen concentrations. Genetics 37: 665– 677. 5 Bonét-Maury, P. 1952. Chemical phenomena in irradiated pure water. Disc. Faraday Soc. 12: 72– 79. 6 Bonét-Maury, P. and Lefort, M. 1948. La formation d'eau oxygénée dans l'eau irradiée par les rayons × et a. Compt. rend. 226: 1363– 1364. 7 Caldecott, R. S., Frolik, E. F. and Morris, R. 1952. A comparison of X-rays and thermal neutrons on dormant seeds of barley. Proc. Nat. Acad. Sci. 38: 804– 809. 8 Ehrenberg, L., Gustafsson, Å. and Nybom, N. 1952. Effects of ionizing radiations in barley. Ark. f. Bot. Ser. 2. Bd. 11 Nr. 17: 557– 568. 9 Ehrenberg, L. and Nybom, N. 1952. Chemical and biological effects of neutrons and X-rays. Hereditas XXXVIII: 481– 501. 10 Forssberg, A. and Nybom, N. 1953. Combined effects of cystein and irradiation on growth and cytology of Allium roots. Physiol. Plant. 6: 78– 95. 11 Giles, N. H., Beatty, A. V. and Riley, H. P. 1952. The effect of oxygen on the production by fast neutrons of chromosomal aberrations in Tradescantia microspores. Genetics 37: 641– 649. 12 Giles, N. H. and Riley, H. P. 1950. Studies on the mechanism of the oxygen effect on the radiosensitivity of Tradescantia chromosomes. Proc. Nat. Acad. Sci. 36: 337– 344. 13 Gustafsson, Å. and Nybom, N. 1949. Colchicine, X-rays and the mutation process. Hereditas XXXV: 280– 284. 14 Hayden, B. and Smith, L. 1949. The relation of atmosphere to biological effects of X-rays. Genetics 34: 26– 43. 15 Kaplan, R. 1951. Chromosomen- und Faktormutationen in Gerstenkörnern bei verschiedenartigen Quellungsbehandlungen oder Kälte während oder nach der Röntgenbestrahlung sowie bei Dosisfraktionierung. Zschr. f. ind. Abst.- u. Vererb.-lehre 83: 347– 382. 16 MacKey, J. 1951. Neutron and X-ray experiments in barley. Hereditas XXXVII: 421– 464. 17 Nybom, N., Gustafsson, Å. and Ehrenberg, L. 1952. On the injurious action of ionizing radiations in plants. Bot. Not. (Lund): 343– 365. 18 Nybom, N., Lundqvist, U., Gustafsson, Å. and Ehrenberc, L. 1953. Biological effects of X-irradiation at low temperatures. Heredilas XXXIX: 445– 457. 19 Thoday, J. M. and Read, J. 1949. Effect of oxygen on the frequency of chromosome aberrations produced by alpha-rays. Nature 163: 133– 134. Citing Literature Volume39, Issue3-4August 1953Pages 493-504 ReferencesRelatedInformation

HereditasVolume 83, Issue 1 p. 134-138 Open Access The modification of alkylation and radiation damage by caffeine Saeed Hussain, Corresponding Author Saeed Hussain Wallenberg Laboratory, Stockholm University, Sweden*Wallenberg Laboratory Lilla Frescati S-10405 Stockholm 50, SwedenSearch for more papers by this authorLars Ehrenberg, Lars Ehrenberg Wallenberg Laboratory, Stockholm University, SwedenSearch for more papers by this authorGunnar AhnstrÖm, Gunnar AhnstrÖm Wallenberg Laboratory, Stockholm University, SwedenSearch for more papers by this author Saeed Hussain, Corresponding Author Saeed Hussain Wallenberg Laboratory, Stockholm University, Sweden*Wallenberg Laboratory Lilla Frescati S-10405 Stockholm 50, SwedenSearch for more papers by this authorLars Ehrenberg, Lars Ehrenberg Wallenberg Laboratory, Stockholm University, SwedenSearch for more papers by this authorGunnar AhnstrÖm, Gunnar AhnstrÖm Wallenberg Laboratory, Stockholm University, SwedenSearch for more papers by this author First published: July 1976 https://doi.org/10.1111/j.1601-5223.1976.tb01579.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Literature cited Ames, B. N. 1971. The detection of chemical mutagens with enteric bacteria. — In Chemical Mutagens: Principles and Methods for their Detection, Vol. 1 (Ed. A. Hollaender Plenum Press, New York, p. 267– 282. Brøgger, A. 1974. Caffeine enhancement of chromosome damage in human lymphocytes treated with methyl-methane-sulphonate, mytomycin C and X-rays. Mutat. Res. 23: 353– 360. Cleaver, J. E. and Thomas, G. H. 1969 Single-strand interruptions in DNA and the effect of caffeine in Chinese hamster cells irradiated with ultraviolet light. Biochem. Biophys. Res. Commun. 36: 303– 308. Domon, M., Barton, B., Forte, A. and Rauth, A. M. 1970. The interaction of caffeine with ultraviolet-light-irradiated DNA. Int. J. Radiat. Biol. 17: 395– 399. Doneson, I. N. and Shankel, D. M. 1964. Mutational synergism between radiations and methylated purines in Escherichia coli. J. Bacteriol. 87: 61– 67. Fries, N. and Kihlman, B. 1948. Fungal mutations obtained with methyl xanthines. Nature 162: 573. Harm, W. 1967. Differential effects of acriflavine and caffeine on various ultraviolet-irradiated Escherichia coli strains and T1, phage. Mutat. Res. 4: 93– 110. Kihlman, B. A. 1974. Effect of caffeine on the genetic material. Mutat. Res. 26: 53– 71. Kihlman, B. A. and Levan, A. 1949. The cytological effect of caffeine. Hereditas 35: 109– 111. Lehman, A. R. and Kirk-Bell, S. 1974. Effect of caffeine and theophylline on DNA synthesis in unirradiated and UV-irradiated mammalian cells. Mutat. Res. 26: 73– 82. Roberts, J. J. and Ward, K. N. 1973. Inhibition of post-replication repair of alkylated DNA by caffeine in Chinese hamster cells but not in HeLa cells. Chem.-Biol. Interact. 7: 241– 264. Turtoczky, I. and Ehrenberg, L. 1969. Reaction rates and biological action of alkylating agents: Preliminary report on bactericidal and mutagenic action in E. coli.. Mutat. Res. 8: 229– 238. Vechet, B. 1968. The enhancement of mutagenic effect of ultraviolet radiation in Escherichia coli by caffeine and acriflavine. Folia Microbiol. 13: 379– 390. Walker, I. G. and Reid, B. D. 1971. Caffeine potentiation of the lethal action of alkylating agents in L-cells. Mutat. Res. 12: 101– 104. Witkin, E. M. 1961. Modification of mutagenesis initiated by ultraviolet light through post-treatment of bacteria with basic dyes. J. Cell. Comp. Physiol. 58 (Suppl. 1): 135– 144. Witkin, E. M. 1969. Ultraviolet induced mutation and DNA repair. Ann. Rev. Genet. 3: 625– 652. Volume83, Issue1July 1976Pages 134-138 ReferencesRelatedInformation

HereditasVolume 55, Issue 2-3 p. 213-226 Open Access GENETIC CHANGES INDUCED BY SEMI-ACUTE γ-IRRADIATION OF POLLEN MOTHER CELLS IN LARIX LEPTOLEPIS (SIEB ET ZUCC.) GORD GÖSTA ERIKSSON, GÖSTA ERIKSSON DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorINGER EKBERG, INGER EKBERG DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorLARS EHRENBERG, LARS EHRENBERG DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorBRANKA BEVILACQUA, Corresponding Author BRANKA BEVILACQUA DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENDepartment of Forest Genetics and Dendrology, Forestry Faculty, University of Zagreb, Yugoslavia.Search for more papers by this author GÖSTA ERIKSSON, GÖSTA ERIKSSON DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorINGER EKBERG, INGER EKBERG DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorLARS EHRENBERG, LARS EHRENBERG DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENSearch for more papers by this authorBRANKA BEVILACQUA, Corresponding Author BRANKA BEVILACQUA DEPARTMENT OF FOREST GENETICS, ROYAL COLLEGE OF FORESTRY, STOCKHOLM 50 INSTITUTE OF RADIOBIOLOGY, UNIVERSITY OF STOCKHOLM, SWEDENDepartment of Forest Genetics and Dendrology, Forestry Faculty, University of Zagreb, Yugoslavia.Search for more papers by this author First published: December 1966 https://doi.org/10.1111/j.1601-5223.1966.tb02049.xCitations: 4AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Literature cited Andersson, G. and Olsson, G. 1954. Svalöf's Primes white mustard—a market variety selected in X-ray treated material. Acta Agric. Scand. 4: 574– 577. Barner, H. and Christiansen, H. 1960. The formation of pollen, the pollination mechanism, and the determination of the most favourable time for controlled pollination in Larix. Silvae Genet. 9: 1– 11. Bauer, R. 1957. The induction of vegetative mutations in Kibes nigrum. Heriditas 43: 323– 337. Blixt, S., Ehrenberg, L. and Gelin, O. 1958. Quantitative studies of induced mutations in peas. I. Methodological investigations. Agri Hort. Genet. 16: 238– 250. Bluket, N. A. 1963. Starch in gymnosperms. Dokladi TSHA 83: 367– 372. Brandenburg, M. K., Mills, H. L., Rickard, W. H. and Shields, L. M. 1962. Effects of acute gamma radiation on growth and morphology in Pinus monophylla. Torr and Frem. (Pinyon pine). — Radiat. Bot. 2: 252– 263. Christiansen, H. 1960. On the effect of low temperature on meiosis and pollen fertility in Larix decidua Mill. Silvae Genet. 9: 72– 78. Davis, T. S. 1962. Effect of cobalt-60 gamma radiation on pine seed and one-year-old seedlings. Forest Sci. 8: 411– 412. Ehrenberg, L. and Eriksson, G. 1964. Mutation in the waxy character in barley pollen grains following 90Sr-incorporation at low activities. Mutat. Res. 1: 139– 145. Ehrenberg, L. and Eriksson, G. 1966. The dose dependence of mutation rates in the rad range, in the light of experiments with higher plants. Acta Radiol. Suppl. 254: 73– 81. Eriksson, G. 1962. Radiation induced reversions of a waxy allele in barley. Radiat. Rot. 2: 35– 39. Eriksson, G. 1963. Induction of waxy mutants in maize by acute and chronic gamma irradiation. Hereditas 50: 161– 178. Eriksson, G. 1965a. The size of the mutated sector in barley spikes estimated by means of waxy mutants. Hereditas 53: 307– 326. Eriksson, G. 1965b. Variations in radiosensitivity during meiosis of pollen mother cells in barley and maize. — Proc. Symp. Mutat. Process, Praha 1965. In press. Eriksson, G. and Tavrin, E. 1965. Variations in radiosensitivity during meiosis of pollen mother cells in maize. Hereditas 54: 156– 169. Gelin, O. E. V. 1954. X-ray mutants in peas and vetches. Acta Agric. Scand. 4: 558– 568. Granhall, I. 1954. Spontaneous and induced bud mutations in fruit trees. Acta Agric. Scand. 4: 594– 600. Gustafsson, Å. The mutation system of the chlorophyll apparatus. Lunds Univ. Årsskr. N.F. 36: 1– 40. Gustafsson, Å. 1962. Polyploidy and mutagenesis in forest-tree breeding. — Proc. 5th World Forestry Congr., p. 793– 805. Gustafsson, Å. 1963. Productive mutations induced in barley by ionizing radiations and chemical mutagens. Hereditas 50: 211– 263. Gustafsson, Å. and Simak, M. 1958. Effect of X- and γ-rays on conifer seed. Medd. Stat. Skogsforskningsinst. 48: 5: 1– 20. Hadley, E. B. and Woodwell, G. M. 1965. Effects of ionizing radiation on rates of CO2 exchange of pine seedlings. Radiat. Res. 24: 650– 656. Mergen, F. and Johansen, T. S. 1963. Effect of ionizing radiation on microsporo-genesis in Pinus rigida Mill. Radiat. Bot. 3: 321– 331. Mergen, F. and Stairs, G. R. 1962. Low level chronic gamma irradiation of a pitch pine-oak forest—its physiological and genetical effects on sexual reproduction. Radiat. Bot. 2: 205– 216. Mergen, F. and Thielges, B. A. 1966. Effects of chronic exposures to Co60 radiation on Pinus rigida seedlings. Radiat. Bot. 6: 203– 210. Mericle, L. W., Mericle, R. P. and Sparrow, A. H. 1962. Cumulative radiation damage in oak trees. Radiat. Bot. 2: 265– 271. Miksche, J. P., Sparrow, A. H. and Rogers, A. F. 1962. The effect of chronic gamma irradiation on the apical meristem and bud formation of Taxus media. Radiat. Bot. 2: 125– 129. Nilsson-Ehle, H. 1938. Darstellung tetraploider Äpfel und ihre Bedeutung für die praktische Apfelzüchtung Schwedens. Hereditas 24: 195– 209. Nybom, N. 1961. The use of induced mutations for the improvement of vegetatively propagated plants. Mutat. Plant Breed. NAS-NRC 891: 252– 294. Ohba, K. 1964. Studies on radiosensitivity and induction of somatic mutations in forest trees. — Gamma Field Symposia No. 3 Mutat. Quant. Traits 1964. Pedigo, R. A. 1963. Effects of ionizing radiation on Pinus taeda L. — Proc. Nat. Symp. Radioecol. 1st, Fort Collins, Colo. Sept. 10–15, 1961, p. 295– 299. Platt, R. R. 1963. Ecological effects of ionizing radiation on organisms, communities and ecosystems. — Proc. Nat. Symp. Radioecol. 1st, Fort Collins, p. 243– 255. Sax, K. and Enzmann, E. V. 1939. Effect of temperature on X-ray-induced chromosome aberrations. Proc. Nat. Acad. Sci. U.S. 25: 397– 405. Schnarf, K. 1941. Vergleichende Cytologie des Geschlechtsapparates der Kormo-phyten. — Berlin . Sparrow, A. H. 1965. Comparisons of the tolerances of higher plant species to acute and chronic exposures of ionizing radiation. Jap. J. Genet. Suppl. 40: 12– 37. Sparrow, A. H., Cuany, R. L., Miksche, J. P. and Schairer, L. A. 1961. Some factors affecting the responses of plants to acute and chronic radiation exposures. Radiat. Bot. 1: 10– 34. Sparrow, A. H. and Gunckel, J. E. 1956. The effects on plants of chronic exposure to gamma radiation from radiocobalt. Proc. Intern. Conf. Peaceful Uses At. Energy, Geneva 1955 12: 52– 59. Sparrow, A. H., Shairer, L. A., Sparrow, R. C. and Campbell, W. F. 1963. The radiosensitivity of gymnosperms. I. The effect of dormancy on the response of Pinus strobus seedlings to acute gamma irradiation. Proc. Intern. Conf. Peaceful Uses At. Energy, Geneva 1955 3: 169– 173. Sparrow, A. H. Schairer, L. A. and Woodwell, G. M. 1965. Tolerance of Pinus rigida trees to a ten-year exposure to chronic gamma irradiation from cobalt-60. Proc. Intern. Conf. Peaceful Uses At. Energy, Geneva 1955 5: 7– 22. Sparrow, A. H. and Woodwell, G. M. 1962. Prediction of the sensitivity of plants to chronic gamma irradiation. Proc. Intern. Conf. Peaceful Uses At. Energy, Geneva 1955 2: 9– 26. Stairs, G. R. 1964. Effects of chronic gamma radiation on seed production in an oak forest. Advancing Frontiers Plant Sci. 9: 207– 216. Swanson, C. P. 1957. Cytology and cytogenetics. — Prentice-Hall. Syrach Larsen, C. and Westergaard, M. 1938. Contributions to the cytogenetics of forest trees. I. A. triploid hybrid between Larix decidua Miller and Larix occi-dentalis Nutt. J. Genet. 36: 523– 530. Wettstein, D. von, Gustafsson, A. and Ehrenberg, L. 1959. Mutationsforschung und Züchtung. — Arbeitsgemeinsch. f. Forsch. Land. Nordrhein — Westf. Ed. L. Brandt. Köln und Opladen. 73: 7– 48, 59–60. Woodwell, G. M. 1962. Effects of ionizing radiation on terrestrial ecosystems. Experiments show how ionizing radiation may alter normally stable patterns of ecosystem behavior. Science 138: 572– 577. Woodwell, G. M. and Miller, L. N. 1963. Chronic gamma radiation affects the distribution of radial increment in Pinus rigida stems. Science 139: 222– 223. Woodwell, G. M. and Sparrow, A. H. 1963. Predicted and observed effects of chronic gamma radiation on a near-climax forest ecosystem. Radiat. Bot. 3: 231– 237. Citing Literature Volume55, Issue2-3December 1966Pages 213-226 ReferencesRelatedInformation

HereditasVolume 56, Issue 2-3 p. 277-305 Open Access ON THE MUTAGENIC ACTION OF ALKANESULFONIC ESTERS IN BARLEY L. EHRENBERG, L. EHRENBERG INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorU. LUNDQVIST, U. LUNDQVIST INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorS. OSTERMAN, S. OSTERMAN INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorB. SPARRMAN, B. SPARRMAN INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this author L. EHRENBERG, L. EHRENBERG INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorU. LUNDQVIST, U. LUNDQVIST INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorS. OSTERMAN, S. OSTERMAN INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this authorB. SPARRMAN, B. SPARRMAN INSTITUTE OF BIOCHEMISTRY, UNIVERSITY OF STOCKHOLM, AND INSTITUTE OF GENETICS, UNIVERSITY OF LUND, SWEDENSearch for more papers by this author First published: December 1966 https://doi.org/10.1111/j.1601-5223.1966.tb02081.xCitations: 9AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume56, Issue2-3December 1966Pages 277-305 ReferencesRelatedInformation

When an environmental factor is tested for mutagenicity or ability to induce related stochastic effects, a negative result of the test is unable, without additional information, to demonstrate non-mutagenicity, etc. The confidence interval of the accepted no-effect might include a response that corresponds to a non-acceptable risk in exposed populations. Tests in microorganisms for genetic toxicity due to non-thermal effects of microwaves and radio-waves, mostly giving negative results, are discussed from these points of view. As a basis for experimental studies (Anderstam et al. 1983, Hereditas 98: 11–32) methods are indicated to estimate the size of a test that would render it able to detect or exclude, with sufficient statistical power, non-acceptable risks due to occupational exposure. This calculation has to take into consideration the ratio of absorbed doses in exposed populations and in experiments, and a translation factor from response in the test system to risk in man. The latter factor was estimated by referring the response in test systems and the risk for cancer or heritable damage in man, to dose-equivalents of γ-radiation. Statistical methods for treatment of experimental data, especially for the purpose of minimizing errors, are discussed.

Values for reaction-kinetic parameters of electrophiles can be used to predict mutagenic potency. One approach employs the Swain-Scott relationship for comparative kinetic studies of electrophilic agents reacting with nucleophiles. In this way glycidamide (GA), the putatively mutagenic/carcinogenic metabolite of acrylamide, was assessed by determining the rates of reaction with different nucleophiles. The rate constants (kNu) were determined using the "supernucleophile" cob(I)alamin [Cbl(I)] as an analytical tool. The Swain-Scott parameters for GA were compared with those of ethylene oxide (EO). The substrate constants, s values, for GA and for EO were found to be 1.0 and 0.93, respectively. The reaction rates at low values of nucleophilic strength (n=1-3), corresponding to oxygens in DNA, were determined to be 2-3.5 times higher for GA compared to EO. GA was also more reactive than EO towards other nucleophiles (n=0-6.4). The mutagenic potency of GA was determined in Chinese hamster ovary cells (hprt mutations in CHO-AA8 cells per dose unit with gamma-radiation as reference standard). The potency of GA was estimated to be about three mutations per 10(5) cells and mMh corresponding to about 40 rad-equ./mMh. A preliminary comparison of the mutagenic potency (per mMh and as rad-equivalents) of GA and EO shows an approximately seven times higher potency for GA. A higher mutagenic potency of GA compared to EO is compatible with expectation from reaction-kinetic data of the two compounds. The data confirmed that GA is not a strong mutagen, which is in line with what is expected for simple oxiranes. The present study shows the value of cob(I)alamin for the determination of reaction-kinetic parameters and their use for prediction of mutagenic potency.

The strongly nucleophilic cob(I)alamin, i.e. Vitamin B12 with Co(III) reduced to Co(I), is introduced as a trapping agent in the determination of concentrations of electrophilic reagents. This compound was applied, in comparison with the previously used moderately reactive nicotinamide (H.J.C.F. Nelis and J.E. Sinsheimer (1981). Anal. Biochem., 115, 151.). Oxiranes, metabolites of 1-alkenes, were chosen as model electrophiles. The reagents (nicotinamide and cob(I)alamin) were evaluated in the determination of the rates of reaction toward valine methylamide, a model of N-terminal valines in hemoglobin often used for monitoring of doses in vivo of genotoxic carcinogens. The rate constants for reaction at 37°C with valine methylamide (k VMA) determined by the cob(I)alamin and nicotinamide procedure, respectively, were for ethylene oxide (1.6, 1.7), propylene oxide (0.9, 1.1), 1,2-epoxybutane (0.7, 0.8) and 1,2-epoxyoctane (0.5, 0.6) M−1 h−1, decreasing with increasing number of carbons of the oxirane. Concentrations of oxiranes trapped with nicotinamide are underrated in reaction mixtures containing valine methylamide due to consumption by reaction with the competing nucleophile, a disturbance that is not observed in trapping with cob(I)alamin which reacts about 105 times faster than nicotinamide. Cob(I)alamin which was demonstrated to be an efficient nucleophile for trapping of electrophiles, also in the presence of competing nucleophiles, is promising as an analytical tool in toxicological studies of reactive compounds. Furthermore, cob(I)alamin can be used to detect, measure and compare electrophilic reactivity of chemical substances, a property that is associated with genotoxic potency.

Background The construction of a railway tunnel through Hallandsås, a mountain ridge in the south-west of Sweden was initiated in 1992. The existing old railway passing this ridge was considered to be a needles eye for railway connections from western Scandinavia to the continent (Fig. 1). A tunnel together with the prospected bridge from Malmö to Copenhagen (completed in year 2000) would be economically important, narrowing Norway and Sweden to the continent.

Cancer risk assessment of polycyclic aromatic hydrocarbons (PAH) is complicated by several of these compounds exerting a promoter action leading to high tumour incidences at high doses. Cancer risks at low doses corresponding to the uptake from air and food in the general environment would best be estimated on the basis of measurement of in vivo target doses of genotoxic (mutagenic) intermediates and a determination of mutation frequency per unit of dose. In experiments ultimately aiming at a risk assessment of environmental PAH from in vivo doses benzo[a]pyrene (BaP) was chosen as a model. gamma-Radiation has earlier been used as a reference standard in cancer risk estimation of genotoxic chemicals where dose equivalents (rad-equivalents) have been shown to give reliable risk estimates for several alkylating agents. Variation in dose of BaP diolepoxide between organs was studied by measurement of deoxyguanosine-N(2) adducts in DNA after administration of BaP by gavage to mice of a strain with reduced DNA repair (Xpa(-/-)). The adduct levels in spleen, forestomach, stomach and small intestine were approximately the same; with the adduct level in spleen as reference it was twice as high in liver and lung and about half as high in colon tissue. A chemical or radiation dose is proportional to the cumulative frequency of putatively premutagenic changes (premutagenic hits) in DNA. The mutation frequency per premutagenic hit (genotoxic chemicals) and per unit of dose (gamma-radiation) were calculated from acutely exposed V79 cells in order to determine the mutagenic effectiveness of each agent. Based on the mutagenic effectiveness determined in this study 10(-4) Gy can be regarded equally effective in causing phenotypically expressed HPRT mutations as the dose of BaP which causes the formation of one deoxyguanosine-N(2) adduct per cell.

Methods for estimating the risks, that is, the probabilities of contracting a disease, are required as a basis of decision-making regarding the needs for protection and risk reduction. A mechanism-based model has been developed for estimating the cancer risks from genotoxic chemicals using adducts to macromolecules for determining the in vivo dose. On the assumption that cancer is caused by an increased frequency of mutations in tissues, interacting with inherited or acquired growth-promoting factors, a simplified model has been proposed for estimating cancer risks from chemically reactive, that is, mutagenic agents. According to a multiplicative model, the risk increment (deltaP) is deltaP = beta x D x P0, proportional to the background incidence (P0) and linearly dependent on dose at low to intermediate doses (D); beta is the risk coefficient, which is approximately the same for different tumor sites and, probably, different species. This model is already in use for ionizing radiation and has been validated for a few mutagenic and carcinogenic chemical compounds. Inherent in this method is the measurement of dose. Sensitive chemical methods have been developed for determining reactive compounds and intermediates in vivo through their stable reaction products (adducts) with proteins, particularly hemoglobin. In humans or animals, the doses of genotoxic agents can be derived from measured levels of adducts and rates of adduct formation. This approach has been applied to various exposures such as air pollutants in occupational settings, carcinogens in foods, and tobacco smoke. By such methods, exposures to previously unknown mutagens and carcinogens may be detected and assessed in humans. Examples of this are epoxides (from endogenously produced alkenes) and compounds (such as acrylamide) formed in cooking foodstuffs.

Diesel fuels, classified as environmentally friendly, have been available on the Swedish market since 1991. The Swedish diesel fuel classification is based upon the specification of selected fuel composition and physical properties to reduce potential environmental and health effects from direct human exposure to exhaust. The objective of the present investigation was to compare the most stringent, environmentally classified Swedish diesel fuel (MK1) to the reference diesel fuel used in the "European Program on Emissions, Fuels and Engine Technologies" (EPEFE) program. The study compares measurements of regulated emissions, unregulated emissions, and biological tests from a Volvo truck using these fuels. The regulated emissions from these two fuels (MK1 vs EPEFE) were CO (-2.2%), HC (12%), NOx (-11%), and particulates (-11%). The emissions of aldehydes, alkenes, and carbon dioxide were basically equivalent. The emissions of particle-associated polycyclic aromatic hydrocarbons (PAHs) and 1-nitropyrene were 88% and 98% lower than those of the EPEFE fuel, respectively. The emissions of semi-volatile PAHs and 1-nitropyrene were 77% and 80% lower than those from the EPEFE fuel, respectively. The reduction in mutagenicity of the particle extract varied from -75 to -90%, depending on the tester strain. The reduction of mutagenicity of the semi-volatile extract varied between -40 and -60%. Furthermore, the dioxin receptor binding activity was a factor of 8 times lower in the particle extracts and a factor of 4 times lower in the semi-volatile extract than that of the EPEFE fuel. In conclusion, the MK1 fuel was found to be more environmentally friendly than the EPEFE fuel.

According to a multiplicative model for prediction of cancer risk for genotoxic agents the incremental cancer risk is, for low-intermediate exposures, proportional to target doses of the genotoxic substance and to the background risk in control groups. This model has been applied to evaluate cancer tests of acrylamide in rodents. Because of its reactivity toward DNA, glycidamide is assumed to be the causative genotoxic metabolite of acrylamide. Evaluation of experimental data according to the multiplicative model shows that mice, compared with rats, are of the order of 10 times more sensitive per administered dose of acrylamide. The US EPA procedure would, however, generally predict rats to be about twice as sensitive as mice to carcinogenic chemicals, because their estimates are based on scaling of the dose per square meter body surface area, as a surrogate for metabolic differences between the species. The comparison of rats and mice with respect to observed cancer incidence is at a key position in the evaluation of the usefulness of risk models for extrapolation between species. In the present study mice and rats were compared, with respect to in vivo doses of acrylamide and the metabolite glycidamide, after exposure to acrylamide. The relative in vivo doses were inferred from levels of hemoglobin adducts. The adduct levels from glycidamide were, per administered dose of acrylamide, approximately 3-10 times higher in mice than in rats. In combination with the above mentioned higher sensitivity of mice than rats in cancer tests of acrylamide this is compatible with the concept that glycidamide is the key genotoxic factor in acrylamide exposure. Furthermore, it is shown that the multiplicative, i.e. relative, risk model and measurements of the dose of the genotoxic factor give good prediction of the observed risk from acrylamide in cancer tests with rats and mice.

Ethylene oxide (EO) is mutagenic in various in vitro and in vivo test systems and carcinogenic in rodents. EO forms different adducts upon reaction with DNA, N7-(2-hydroxyethyl)guanine (N7-HEG) bring the main adduct. The major objectives of this study were: (a) to determine the formation and persistence of N7-HEG adducts in liver DNA of adult male rats exposed to 0, 50, 100 and 200 ppm by inhalation (4 weeks, 5 days/week, 6 h/day) and (b) to assess dose-response relationships for Hprt gene mutations and various types of chromosomal changes in splenic lymphocytes.N7-HEG adducts were measured 5, 21, 35 and 49 days after cessation of exposure. By extrapolation, the mean concentrations of N7-HEG immediately after cessation of exposure ('day 0') to 50, 100 and 200 ppm were calculated as 310, 558 and 1202 adducts/10(8) nucleotides, respectively, while the mean concentration in control rats was 2.6 adducts/10(8) nucleotides. Ar 49 days, N7-HEG values had returned close to background levels. The mean levels of N-(2-hydroxyethylvaline) adducts in haemoglobin were also determined and amounted 61.7, 114 and 247 nmol/g globin, respectively.Statistically significant linear relationships were found between mean N7-HEG levels ('day 0') and Hprt mutant frequencies at expression times 21/22 and 49/50 days and between mean N7-HEG ('day 0') and sister-chromatid exchanges (SCEs) or high frequency cells (HFC) measured 5 days post-exposure. At day 21 post-exposure, SCEs and HFCs in-part persisted and were significantly correlated with persistent N7-HEG adducts. No statistically significant dose effect relationships were observed for induction of micronuclei, nor for chromosome breaks or translocations.In conclusion, this study indicates that following sub-chronic exposure, EO is only weakly mutagenic in adult rats. Using the data of this study to predict cancer risk in man resulting from low level EO exposures in conjunction with other published data, i.e., those on (a) genotoxic effects of EO in humans and rats, (b) DNA binding of other carcinogens, (c) natural background DNA binding and (d) genotoxic potency of low energy transfer (LET) radiation, it is not expected that long term occupational exposure to airborne concentrations of EO at or below 1 ppm EO produces an unacceptable increased risk in man. (C) 2000 Elsevier Science B.V. All rights reserved.

The supernucleophilic cobalt compound, cob(I)alamin, has been kinetically characterized with respect to its ability to bring about transalkylation of adducts to DNA phosphates (phosphotriesters). The reactivity of cob(I)alamin toward different phosphotriesters (model compounds and methylated DNA), as well as its specificity toward DNA-phosphate adducts, has been investigated. Through nucleophilic displacement on the alkyl by cob(I)alamin, the alkyl groups (methyl and ethyl) were transferred from phosphotriesters within minutes at room temperature. In contrast, methylated nucleosides (base adducts) were stable in the presence of cob(I)alamin.

A mechanistic model and associated procedures are proposed for cancer risk assessment of genotoxic chemicals. As previously shown for ionizing radiation, a linear multiplicative model was found to be compatible with published experimental data for ethylene oxide, acrylamide, and butadiene. The validity of this model was anticipated in view of the multiplicative interaction of mutation with inherited and acquired growth-promoting conditions. Concurrent analysis led to rejection of an additive model (i.e. the model commonly applied for cancer risk assessment). A reanalysis of data for radiogenic cancer in mouse, dog and man shows that the relative risk coefficient is approximately the same (0.4 to 0.5 percent per rad) for tumours induced in the three species.

This report presents results from a project which had the aim of investigating the potential environmental and health impact of emissions from ethanol ethanol blended diesel fuels and to compare these with neat diesel fuels. The exhaust emissions were characterised regarding regulated exhaust components, particulate and semivolatile Polycyclic Aromatic Hydrocarbons (PAC) and with bioassays. The bioassays were mutagenicity ana TCDD receptor affinity tests. Results: Neat ethanol fuels are "low emission fuels", while European diesel fuel quality (EDF) and an ethanol blended EDF are "high emission" fuels. Other fuels, such as Swedish Environmental Class one (MK1) and an ethanol blended MK1, are "intermediate fuels" regarding emissions. When using an oxidising catalyst exhaust aftertreatment device a reduction of harmful substances in the exhaust emissions was found. The relatively low emission of PAH from ethanol fuelled engines would indicate a lower cancer risk from ethanol than from diesel fuels.

The reactive diol epoxides of fluoranthene and benzo[a]pyrene, (+/-)-anti-c-I,c-10b-epoxy-1,2,3,10b-tetrahydrofluoranthene-r-2,t-3-diol (1) and (+/-)-anti-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-r-7,t-8-diol (4), respectively, are known genotoxic agents and effective alkylators of nucleophilic sites in DNA and proteins. As models of in vivo N-alkylation at the N-termini of hemoglobin (Hb), N-L-valine methylamide (VMA) products of 1 and 4 were synthesised, N-(r-1,c-2,t-3-trihydroxy-1,2,3.10b-tetrahydrofluoranthen-t-10b-yl)-L-valine methylamide (2a,b) and N-(r-7,t-8,t-9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyren-c-10-yl)-L-valine methylamide (5a,b), respectively. For isolation of the reaction products from the alkylation of VMA two reversed-phase HPLC systems were developed. From each diol epoxide two diastereoisomeric products were isolated in separate fractions. The products were characterised by H-1 NMR spectroscopy as well as by thermospray (TSP) tandem quadrupole mass spectrometry (MS and MS/MS) and fluorescence. When analysed by TSP-MS/MS the quasimolecular ions, [M+H](+), have a neutral loss of either the VMA or the 1 and 4 adduct moieties, respectively. The major daughter ion from 5a,b is the adduct moiety and the corresponding ion from 2a,b is the VMA moiety. Minor daughter ions are, in both cases, [(M-VMA)H+](+) ions with additional loss of H2O or H2O+CO. The higher the number of hydroxy groups in the 2a,b ions, the more easily is the C10b-amino bond disrupted in collision-induced dissociation.

4,4'-Methylenedianiline (MDA) is a widely used mutagenic and carcinogenic industrial chemical. It is also a metabolite of 4,4'-methylenediphenyl diisocyanate (MDI), which is used in the manufacturing of polyurethane foams. Biomonitoring of MDA, like other aromatic amines, is mainly carried out by GC/MS measurement of cysteine adducts in Hb from the nitroso metabolite, released by alkaline hydrolysis. In the present study it was investigated whether the formation of Hb adducts from non-nitroso metabolites of MDA can be used for the dosimetry of MDA. The study was carried out by treatment of mice with MDA and tritiated MDA or deuterated MDA and by identification of their products of reaction with Hb, after enzymatic hydrolysis of the globin and enrichment of the adducts. The main adduct, about 50% of the total amount of MDA associated with Hb, was characterized by MS and was shown to be a reaction product of MDA and the amino group of N-terminal valine in Hb, the derived structure being 1-[(4-imino-2,5-cyclohexadien-1-ylidene)methyl]benzene-4-azo-2-isovaleric acid. It is likely that this quinonoid MDA imine adduct to valine was formed by an attack of a metabolite formed through peroxidative oxidation of MDA, in analogy with earlier observed oxidation of some other aromatic amines, e.g., benzidine. The reactive intermediate is suggested to be [(4-imino-2,5-cyclohexadien-1-ylidene)methyl]-4-aminobenzene. The formation of the adduct was confirmed by incubating MDA with valine methyl ester in vitro in the presence of H2O2 and lactoperoxidase. Further, the same adduct was detected in MDI-exposed and control rats, the level in the exposed animals being about 60 times higher than in the controls. This study indicates that, at least in the mouse, extrahepatic peroxidative metabolism is an important pathway for the bioactivation of MDA, possibly leading to a genotoxic reactive intermediate. This study also demonstrates the usefulness of Hb adduct analysis for the identification of reactive intermediates in vivo.