Polycyclic hydrocarbons induction of diphtheria toxin-resistant mutants in human cells

Stable spontaneous mutants resistant to diphtheria toxin are present in the human cell line (EUE) at a frequency of 0-8 x 10(-6). Mutation increases by a number of polycyclic hydrocarbons have been used as an estimate of their carcinogenic potency. Eight polycyclic hydrocarbons of decreasing carcinogenic potency were assayed: 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene, benz[a]anthracene, dibenz[a,c]anthracene, dibenz[a,h]anthracene, chrysene, anthracene, and a well known mutagenic substance, ethyl methanesulfonate. In our system, which does not require an exogenous source for metabolic activation, the most potent hydrocarbons, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene and benzo[a]pyrene revealed a strong mutagenic effect, whereas three non-carcinogenic hydrocarbons, anthracene, benz[a]anthracene and chrysene were not mutagenic. Our results indicate that there is a relationship between mutagenesis and carcinogenic potency for the tested polycyclic hydrocarbons. The maximum recovery of diphtheria toxin mutants was observed after an expression time of three weeks, corresponding to 10 cell generations.