CHEMICAL CARCINOGENS PRODUCE MUTATIONS TO OUABAIN RESISTANCE IN TRANSFORMABLE C3H-10T1-2 CL 8 MOUSE FIBROBLASTS

Chemical carcinogens induce mutations to ouabain resistance in the transformable mouse fibroblast cell line C3H/10T1/2 Cl 8. The mutant phenotype is stable and heritable in the absence of selective agent, and dose-response curves for mutant frequency were obtained with N-methyl-N'-nitro-N-nitrosoguanidine, 3-methylcholanthrene, benzo[a]pyrene, N-acetoxy-N-2-acetylaminofluorene, and the anti-7,8-diol-9,10-epoxide of benzo[a]pyrene. The ratio of the malignant transformation frequency to the mutation frequency was 12 for benzo [a]pyrene and 21 for N-acetoxy-N-2-acetylaminofluorene. The development of the mutational assay reported here allows the use of this permanent cell line for comparison of mutation and transformation frequencies and as a screening system for xenobiotics that pose mutagenic or carcinogenic hazards to mammalian cells.