Effect of a Tumor Promoter on DNA Repair After Treatment of C3H/10T½ Cells with a Carcinogen
The mechanism by which tumor promoters act is still unknown. Since the initiating carcinogens are believed to interact with the cellular DNA finally resulting in mutations, tumor promoters could act through interference with DNA repair. In this work we investigated the effect of 12-0-tetradecanoyl-phorbol–13-acetate (TPA) on repair synthesis after 20-methylcholanthrene (MCA) treatment. Both in early and in late logarithmic growth phase of C3H/10Tl/2 cells an inhibition of repair synthesis was observed when the cells were exposed to 0.17 μM TPA. The damage introduced by 2 μM MCA exposure for 24 hrs was present 20 hrs later at nearly 0-hrs level in TPA treated cells, while repair synthesis was reduced to 60% in cells not exposed to TPA. At least one of the effects of TPA therefore seems to be an inhibition of DNA repair.
KeywordsTumor Promoter Repair Synthesis Basal Medium Eagle Mouse Embryo Fibroblast Cell Late Logarithmic Growth Phase
Unable to display preview. Download preview PDF.
- 1.I. Bernblum, Sequential aspects of chemical carcinogenesis, in: “Skin Cancer”. Vol. 1 p. 323, F. F. Becker, ed., Plenum Publishing Corp. New York (1975).Google Scholar
- 3.S. Mondal, Two stage carcinogenesis: Possible role of promoters, in: “Genetic differences in chemical carcinogenesis”, R. Kouri, ed., CRC Critical Rev. Toxicol. (in press)(1979).Google Scholar
- 4.I. B. Weinstein, M. Wigler, P. B. Fisher, E. Siskin, and C. Pietropolo, Cell culture studies on the biologic effects of tumor promoters, in: “Carcinogenesis” Vol. 2, p. 313, ed., T.J. Slaga, A. Sivak, and R. K. Boutwell, Raven Press, New York (1978).Google Scholar
- 6.E. Hecker, Isolation and characterization of the co-carcinogenic principles from Croton oil, in: “Methods in Cancer Research”, Vol. 6, p. 439, ed., H. Buch, Academic Press, New York (1971).Google Scholar
- 13.A. R. Petersen, S. Mondal, D. W. Brankow, W. Thon, and C. Heidelberger, Effects of promoters on DNA synthesis in C3H/10T1/2 mouse fibroblasts, Cancer Research, 37: 3223 (1977).Google Scholar