We demonstrate here that tobacco particulate matter (TPM) produced from both non-ventilated and ventilated cigarettes of varying tar contents induced structural and numerical aberrations in cultured Chinese hamster cells. Our data indicate that TPM from ventilated cigarettes is of lower potency in inducing both clastogenic and aneugenic effects compared with TPM from non-ventilated cigarettes. These observations provide support for the concept that the genotoxic activity (to cultured Chinese hamster cells) of cigarette smoke is reduced by increased ventilation to a greater extent than a 1:1 ratio between yield reduction and smoke dilution.

The effects of 1,6-dinitropyrene (1,6-DNP) on the fidelity of cell division were studied in the transformed human fibroblast cell line MRC5VA. Over a dose range of 0.1–10 μg/ml of 1,6-DNP, we observed significant increases in the levels of abnormal division stages, associated with damage to the spindle apparatus of the cell. Qualitative changes in spindle morphology and a quantitative decrease in pole-to-pole spindle length were also observed with increasing doses of 1,6-DNP. Such changes in the size and morphology of the spindle corresponded with an accumulation of cells blocked at metaphase. The presence of catalse did not modify the response, suggesting that the effects on the spindle apparatus and cell division were not caused by the generation of radicals but by the direct action of 1,6-DNP.

Low passage-number cultured Chinese hamster cells were used to assess the ability of four benzodiazepines, namely diazepam, medazepam, midazolam and bromazepam, to induce numerical and structural chromosome aberrations. It was observed that diazepam, medazepam and midazolam treatment produced dose-dependent reductions in the number of diploid cells, with medazepam and midazolam inducing significant levels of hyperdiploidy and diazepam inducing low levels of hypodiploidy (at toxic doses). In contrast, bromazepam-treated cultures showed no significant changes in the level of aneuploidy even when exposed to toxic concentrations. All four sedatives were seen to induce low levels of chromosome aberrations, with bromazepam showing the most potent effect (albeit at a single toxic dose). These observations indicate that these structurally related benzodiazepines could be regarded as potentially genotoxic.

Tobacco particulate matter (TPM) derived from an experimental low to middle tar cigarette was tested for its cytogenetic activity upon a low passage number Chinese hamster pulmonary cell line. Examination of the mitotic profiles (after one cell cycle) revealed no interference by the agent with mitotic spindle formation and/or function. However, complete chromosomes (or parts of them) were seen to dislocate from the mitotic spindles. Such an event was probably the result of the chromosome aberrations, substantial numbers of which were observed in second division cells, or through a process of centromere inactivation. In second division cells there was a reduction in the number of diploid cells accompanied by an increase in both hypodiploidy and polyploidy and there was also a non-dose-related increase in endoreduplication. The results demonstrate that TPM was capable of inducing both structural and numerical chromosome aberrations in cultured mammalian cells.

The ability of 1,6-dinitropyrene to induce chromosome damage in peripheral human lymphocyte cultures has been demonstrated. Low levels of clastogenic activity were detected following 3-h treatments with 1,6-dinitropyrene in the presence of a rat-liver cytosol fraction. The clastogenic activity reached a peak at a concentration of 1.25 μg/ml of 1,6-dinitropyrene after which the frequency of aberrations decreased. This unusual genotoxic dose response is similar to that found previously in yeast and rat-liver cells. The fact that a positive result was obtained using human lymphocytes shows that, in the presence of the appropriate activation system, dinitropyrene is genotoxic in human cells.

T1 proton relaxation times were measured for the halomethanes (CH2Cl2, CH3,Cl, CH2Br2, CH3,Br, CH2I2, CH3I) at room temperature as a function of concentration in CS2. The data were extrapolated to infinite dilution. Experimental dipolar correlation times were computed from the extrapolated relaxation times assuming the intramolecular dipolar mechanism. In contrast to previous results for the chloroethanes, the experimental correlation times did not increase with increasing halogen substitution for corresponding halides. Temperature-dependent T1 studies on CS2 solutions of CH3Br and CH2Br2 showed that the spin-rotation mechanism is an important relaxation mechanism at room temperature. After correctly accounting for the spin-rotation contribution to relaxation, the resulting dipolar correlation times increased with increasing halogen substitution. The experimental results indicated that the methylene halide reorientation can be described by a diffusional model, whereas the methyl halide reorientation can best be described by an inertial model.

Nitropyrenes are a class of polycyclic hydrocarbons that have been shown to be potent point mutagens in the Salmonella/mammalian microsome assay. However, relatively few data have been published on their ability to induce chromosome aberrations. In this paper we report the cytogenetic activity of 1-nitropyrene, 1-nitrosopyrene, and 1-aminopyrene in cultured Chinese hamster cells (Don:Wg3h). Following treatment with 1-nitrosopyrene, high levels of both chromosome and chromatid types of aberrations were induced, the most notable effect being an increase in chromatid exchanges. Much weaker, but statistically significant, responses were also obtained for 1-nitropyrene and 1-aminopyrene.

4 benzodiazepine sedatives, namely diazepam, medazepam, midazolam and bromazepam were investigated for their effects upon the fidelity of cell division in both low passage number and immortalised Chinese hamster cell lines. The study revealed substantial differences in the effect of these structurally related drugs upon mitosis, which may reflect different mechanisms of action of the drugs in cultured cells.

The industrial chemical Michler's ketone (MK) has been examined for its ability to induce abnormalities of mitotic cell division and the production of chromosomal aberrations and aneuploidy. MK was shown to produce aberrant cell division stages in cultured mammalian cells probably by interference with centrosome replication leading to the production of monopolar spindles during metaphase, and multipolar telophase spindles, in the first division after exposure. Cells in the second division after exposure to MK showed increased levels of chromosome aneuploidy which is presumed to result from aberrant cell division. There was also some evidence of increased levels of chromosome structural aberrations at concentrations of 1.5 microgram/ml.

Cultured Chinese hamster liver fibroblast cells were treated with BZD, DAT, DAB and CDA (Sample A), to detect the induction of mitotic spindle defects and aneuploidy. BZD, DAT and DAB induced spindle defects and/or aneuploidy.