Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Purpose/Objective: Ceil cycle checkpoints are thought to play a vital role in radiation resistance. Cell cycle delays at GlLS and G2/M allow cells to repair DNA damage prior to synthesis and mitosis, respectively. The retinoblastoma gene product (pRb), is implicated in the regulation of all phases of the cell cycle and plays a role in apoptosis following ionizing radiation. We investigated the effects caused by inactivation of pRb on the cell cycle, rate of apoptosis and survival following ionizing radiation.

BioEssaysVolume 16, Issue 6 p. 393-394 What the Papers Say Cellular epigenetics and the origin of cancer Scott Cuthill, Scott Cuthill The CRC Beatson Laboratories, Switchback Road, Garscube Estate, Bearsden, Glasgow G61 1BD, U.KSearch for more papers by this author Scott Cuthill, Scott Cuthill The CRC Beatson Laboratories, Switchback Road, Garscube Estate, Bearsden, Glasgow G61 1BD, U.KSearch for more papers by this author First published: June 1994 https://doi.org/10.1002/bies.950160606Citations: 5AboutPDF ToolsRequest permissionExport 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 onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Bishop, J. M. (1991). Molecular themes in oncogenesis. Cell 64, 235–248. 2 Kennedy, A. R., Fox, M., Murphy, G. and Little, J. B. (1980). Relationship between X-ray exposure and malignant transformation in C3H 10T1\2 cells. Proc. Natl Acad. Sci. USA 77, 7262–7266. 3 Mondal, S. and Heidelberger, C. (1970). In vitro malignant transformation by methyl cholanthrene of the progeny of single cells derived from C3H mouse prostate. Proc. Natl Acad. Sci. USA 65, 219–229. 4 Mintz, B. and Illmensee, K. (1975). Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl Acad. Sci. USA 72, 3585–3589. 5 Lavrovsky, V. A., Guvakova, M. A. and Lavrovsky, Y. V. (1992). High frequency of tumour cell reversion to non-tumorigenic phenotype. Eur. J. Cancer 28, 17–21. 6 Chow, M., Yao, A. and Rubin, H. (1994). Cellular epigenetics: Topochronology of progressive ‘spontaneous’ transformation of cells under growth constraint. Proc. Natl Acad. Sci. USA 91, 599–603. 7 Rubin, A. L., Yao, A. and Rubin, H. (1990). Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity. Proc. Natl Acad. Sci. USA 87, 482–486. 8 Rubin, H. and Xu, K. (1989). Evidence for the progressive and adaptive nature of spontaneous transformation in the NIH 3T3 cell line. Proc. Natl Acad. Sci. USA 86, 1860–1864. 9 Rubin, A. L., Arnstein, P. and Rubin, H. (1990). Physiological induction and reversal of focus formation and tumorigenicity in NIH 3T3 cells. Proc. Natl Acad. Sci. USA 87, 10005–10009. 10 Grundel, R. and Rubin, H. (1991). Effect of interclonal heterogeneity on the progressive, confluence-mediated aquisition of the focus-forming phenotype in NIH 3T3 populations. Cancer Res. 51, 1003–1013. 11 Frankfurt, O. S. and Raitcheva, E. (1973). Fast onset of DNA syntheis stimulated by tumour promoter in mouse epidermis at the initiation stage of carcinogenesis. J. Natl Cancer Inst. 51, 1861–1864. 12 Zhang, R., Haag, J. and Gould, M. N. (1990). Quantitating the frequency of initiated cells in in situ NMU-exposed mammary gland. Proc. Am. Assoc. Cancer Res. 31, 138–144. 13 Farber, E. (1976). The pathology of experimental liver cell cancer. In Liver Cell Cancer (ed. H. Warwick), pp. 243–277. Amsterdam, Elsevier/North Holland Biomedical Press. 14 Haddow, A. (1938). Cellular inhibition and the origin of cancer. Acta Unio Intern. Contra Cancrum. 3, 342–352. Citing Literature Volume16, Issue6June 1994Pages 393-394 ReferencesRelatedInformation