Abstract
When Escherichia coli is chronically exposed to very low, nontoxic doses of a monofunctional alkylating agent (notably N-methyl-Nā²-nitro-nitrosoguanidine, MNNG), the adaptive DNA repair pathway is induced which enables the bacteria to resist the killing and mutagenic effects of further alkylation damage1ā3. Mutation resistance in adapted bacteria is achieved, at least partly, by a greatly increased capacity of the cells to eliminate the minor DNA alkylation product O6-methyl-guanine4ā6, which has been strongly implicated as premu-tagenic7,8 and precarcinogenic9. We now show that the chronic treatment of a Chinese hamster ovary (CHO) and a SV40-transformed human skin fibroblast (GM637) cell line with non-toxic levels of MNNG renders the cells resistant to the induction of sister chromatid exchange (SCE) by further alkylation damage. CHO cells also become resistant to killing (GM637 cells have not yet been tested). Having ruled out explanations such as changes in cell cycle distribution, mutagen permeability and mutagen detoxification, we conclude that resistance is probably achieved by the cells becoming more efficient at repairing alleviation damage, analogous to the adaptive response of E. coli1.
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References
Samson, L. & Cairns, J. Nature 267, 281ā283 (1977).
Jeggo, P., Defais, M., Samson, L. & Schendel, P. Molec. gen. Genet. 157, 1ā9 (1977).
Jeggo, P., Defais, M., Samson, L. & Schendel, P. Molec. gen. Genet. 162, 299ā305 (1978).
Schendel, P. F. & Robins, P. E. Proc. natn. Acad. Sci. U.S.A. 75, 6017ā6020 (1978).
Robins, P. & Cairns, J. Nature 280, 74ā76 (1979).
Karran, P., Lindahl, T. & Griffin, B. Nature 280, 76ā77 (1979).
Loveless, A. Nature 223, 206ā207 (1969).
Gerchman, L. L., Ludlum, D. B. Biochim. biophys. Acta 308, 310ā316 (1973).
Goth, R. & Rajewsky, M. F. Proc. natn. Acad. Sci. U.S.A. 71, 639ā643 (1974).
Montesano, R., Bresil, H. & Margison, G. P. Cancer Res. 39, 1798ā1802 (1979).
Montesano, R., Bresil, H., Planche-Martel, G., Margison, G.P. & Pegg, A. E. Cancer Res. 40, 452ā458 (1980).
IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans Vol. 1, 95ā106 (International Agency for Research on Cancer, Lyon, 1972).
Schendel, P. F., Defais, M., Jeggo, P., Samson, L. & Cairns, J. J. Bact. 135, 466ā475 (1978).
Carrano, A. V., Thompson, L. H., Lindl, P.A. & Minkler, J. L. Nature 271, 551ā553 (1978).
Wolff, S., Rodin, B. & Cleaver, J. E. Nature 265, 347ā349 (1977).
Jensen, E. M., LaPolla, R. J., Kirby, P. E. & Haworth, S. R. J. natn. Cancer Inst. 59, 941ā944 (1977).
Lawley, P. D. & Thatcher, C. J. Biochem. J. 116, 693ā707 (1970).
Barranco, S. C. & Humphrey, R. M. Mutat. Res. 11, 421ā429 (1971).
MacRae, W. K., MacKinnon, E. A. & Stich, H. F. Chromosoma 72, 15ā22 (1979).
Wheeler, G. P. & Bowdon, B. J. Biochem. Pharmac. 21, 265ā267 (1972).
DasGupta, U. B. & Summers, W. C. Proc. natn. Acad. Sci. U.S.A. 75, 2378ā2381 (1978).
Sarasin, A. & Benoit, A. Mutat. Res. 70, 71ā81 (1980).
Wolff, S. & Rodin, B. Science 200, 543ā545 (1978).
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Samson, L., Schwartz, J. Evidence for an adaptive DNA repair pathway in CHO and human skin fibroblast cell lines. Nature 287, 861ā863 (1980). https://doi.org/10.1038/287861a0
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DOI: https://doi.org/10.1038/287861a0
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