Relationships Between Aryl Hydrocarbon Hydroxylase Inducibility and Sensitivity to Chemically Induced Subcutaneous Sarcomas in Various Strains of Mice23

Abstract

Among 14 strains of mice, a direct correlation was observed between sensitivity to 3-methylcholanthrene (MCA)-induced and subcutaneous tumors and the hepatic inducibility of one of the hydrocarbon-metabolizing enzyme systems, aryl hydrocarbon hydroxylase (AHH). Every strain showing a carcinogenic index (a measure of sensitivity to chemical carcinogens) >64 was inducible for AHH and every strain with an index of <31 was noninducible. Closer examination involving 8 strains indicated that strain sensitivity was consistent over a wide range of MCA concentrations, but was not consistent when benzo[α]pyrene or 7,12-dimethylbenz[α]anthracene were used as carcinogens. Most strains that were noninducible and insensitive to MCA-induced tumors also exhibited a high incidence of type-C RNA virogene expression, as demonstrated by the group-specific antigen characteristic of these viruses. On the other hand, strains showing a low incidence of virogene expression were usually inducible for AHH and sensitive to MCA-induced tumors. The results support the idea that certain chemical carcinogens are metabolically activated to a carcinogenic intermediate and indicate that the AHH system plays a role in this activation.