Abstract
Observations from various biological systems suggest that chemical carcinogens transform cells by causing somatic mutations through interacting with DNA1–5. These observations raise several fundamental questions regarding the nature of the transforming genes that are the target of the carcinogens. For example, are there unique target gene(s) for chemical carcinogens, or are there multiple potential targets, any of which, when altered, can induce the transformed phenotype? This problem has been approached previously by comparing the rate of transformation by chemical carcinogens with the rate of appearance of dominant mutations in unique cellular genes encoding selectable markers. The results suggested a limited number of targets for transformation, since transformation occurred at a rate that was only 10–100 times greater than the appearance of ouabain-resistant mutants6–8. These results, however, are only rough estimates, because the optimal conditions for induction of transformation and the induction of mutations are known to differ6. In addition, lesions other than point mutations caused by carcinogens, such as frame-shifts, may induce transformation efficiency but not ouabain resistance. We now present an alternative experimental approach to estimating the number of targets for chemical carcinogens, based on the fact that DNAs of certain chemically transformed cell lines can induce the appearance of foci when transferred on to NIH3T3 cells9. These DNAs were treated with a variety of restriction endonucleases before testing their transforming activities by DNA transfer. We have found the same pattern of sensitivity and resistance to inactivation by different endonucleases in all DNAs studied, suggesting that the same transforming gene is being transferred in all cases.
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Shilo, BZ., Weinberg, R. Unique transforming gene in carcinogen-transformed mouse cells. Nature 289, 607–609 (1981). https://doi.org/10.1038/289607a0
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DOI: https://doi.org/10.1038/289607a0
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