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pubmed-article:8022436pubmed:abstractTextTransfection of specific genes into cells capable of expressing chemically induced morphological cell transformation provides a valuable approach to study the mechanisms of action of carcinogens. A human cytochrome P450 isozyme, CYP2A6, has been successfully expressed from a retroviral vector in transformable C3H/10T1/2 (10T1/2) mouse embryo fibroblasts and these resulting 10T1/2 clones were evaluated for the cytotoxic and transforming activities of two nitrosamines, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosodiethylamine (DEN). 10T1/2 clone 29 cells, which expressed high levels of CYP2A6 activity, were responsive to the cytotoxic and morphological transforming effects of DEN or NNK on a concentration-related basis. In 10T1/2 clone 29 cells, DEN at 600 micrograms/ml decreased cell survival to 67%, and induced 0.5 type II&III foci/dish. NNK at 400 micrograms/ml administered to 10T1/2 clone 29 cells decreased survival to 57% and induced 0.43 type II&III foci/dish. Wild-type 10T1/2 cells and 10T1/2 clone 4 cells (infected with the vector but not expressing the CYP2A6 activity) were unresponsive. These results indicate that expression of a cDNA coding for cytochrome P450 in 10T1/2 cells can provide information about the role of the enzyme in the activities of chemical carcinogens and also increase the sensitivity of 10T1/2 cells to a larger number of classes of chemical carcinogens.lld:pubmed
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pubmed-article:8022436pubmed:articleTitleN-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced morphological transformation of C3H/10T1/2CL8 cells expressing human cytochrome P450 2A6.lld:pubmed
pubmed-article:8022436pubmed:affiliationCarcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.lld:pubmed
pubmed-article:8022436pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:8022436pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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