This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peterson, A. R. Articles by Heidelberger, C. Search for Related Content PubMed PubMed Citation Articles by Peterson, A. R. Articles by Heidelberger, C.

Oncogenic Transformation and Mutation of C3H/10T Clone 8 Mouse Embryo Fibroblasts by Alkylating Agents¹

University of Southern California Comprehensive Cancer Center, Cancer Research Laboratory, Los Angeles, California 90033

Two-hr treatments with N-methyl- and N-ethyl-N'-nitro-N-nitrosoguanidines and ethyl methanesulfonate induced ouabain-resistant mutants in C3H/10T cells. The alkylnitronitrosoguanidines gave linear dose-response curves and were more potent mutagens than were ethyl methanesulfonate and methyl methanesulfonate. These differences in potency were largely due to differences in the half-lives of the alkylating agents in culture medium. Differences in mutation frequencies at equitoxic concentrations of the alkylating agents are considered to reflect differences in the chemical mechanisms of alkylation and mutagenesis by the compounds. However, the frequencies of mutations produced at equitoxic concentrations were not uniformly associated with the nucleophilic selectivities of the compounds as expressed by their published Swain-Scott substrate constants. Whether or not followed by repeated replating, the yield of oncogenically transformed foci of asynchronous cells after treatment with the alkylating agents was so low that we could not obtain dose-response curves, and the yield may not be significant. By contrast, in previous experiments with N-methyl-N'-nitro-N-nitrosoguanidines and polycyclic hydrocarbons in Syrian hamster embryo fibroblasts and with ultraviolet light and polycyclic hydrocarbons in C3H/10T cells, transformation occurred to an equal or greater extent than mutation measured in the same cells.

¹ Supported by Grant CA-21036 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 10/10/80. Accepted 5/ 7/81.