Induction of mutation to ouabain resistance and of malignant transformation by chemicals in cloned mouse M2 fibroblasts

Malignant transformation and mutation to ouabain-resistanceis induced in cloned M2 mouse fibroblasts in vitro by treatmentwith N-methyl-N'-nitro-N-nitrosoguanidine and two derivativesof polycyclic aromatic hydrocarbons, the 3, 4-diol derived from7-methylbenz[a]anthracene and the 7, 8-diol-9, 10-oxide derivedfrom benzo[a]pyrene. Transformation is an event more frequentthan mutation, the ratio of transformation to mutation frequenciesvaried between 24 and 1118. Another hydrocarbon derivative,the 9, 10-diol-7, 8-oxide derived from ben-zo[a]pyrene, didinduce ouabain-resistance without causing transformation. Inducedouabain-resistant clones did not behave like transformants,and transformants did not exhibit ouabain resistance. The significanceof these findings is discussed.