Evidence that Benzo(a) pyrene-resistant, aryl hydrocarbon hydroxylase-deficient variants of mouse hepatoma line, Hepa-1, are mutational in origin.

Treatment of Hepa-1 with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, UV light, or ICR-191G, increased the frequency of benzo(a)pyrene-resistant (BPr) clones. The relative efficacies of the mutagens at increasing the frequency of BPr clones correlated with their efficacies a inducing 6-thioguanine-resistant clones. Evidence was obtained that the mutagens induced the BPr variants rather than selecting for BPr cells that preexisted in the treated cultures. All variants tested had reduced AHH activities and phenotypes that were stable over time in culture. Certain "leaky" variants with residual AHH activities and low cloning efficiencies in BP were further selected in BP and subclones isolated. Half the subclones were indistinguishable from their parents, while the majority of the remainder retained at least half of their parents' AHH activity. The marked stability of the phenotype of the variants, and their induction by mutagens, suggests that they are bona fide mutants.