Protection against tumorigenesis by 3-methylcholanthrene in mice by beta-naphthoflavone as a function of inducibility of methylcholanthrene metabolism.

The noncarcinogenic enzyme inducer beta-naphthoflavone (beta-NF) causes an increase in both rate of activation and of detoxification of polycyclic aromatic hydrocarbon carcinogens in tissues of mice of induction-responsive strains. An experiment was carried out to test whether pretreatment with beta-NF would potentiate, protect against, or have no effect on the tumorigenicity of methylcholanthrene (MC) administered intragastrically to mice of varying responsiveness to induction of MC metabolism. The mouse strains used were C57BL/6, BALB/c, and C3H (inbred, highly responsive to induction), Swiss (random-bred, moderately responsive), and DBA/2 and AKR (inbred, nonresponsive). Twelve weekly treatments with 20 mg MC/kg intragastrically were preceded 24 h earlier each week by 150 mg beta-NF/kg i.p. or oil. Mice were killed when moribund or 1 year after start of treatment. During this period the beta-NF-pretreatment greatly reduced mortality due to cancer among the responsive inbred mice, by 100% for the C57BL/6, 89% for the BALB/c, and 65% for the C3H, compared with 50% for the Swiss, 23% for the DBA/2 and 0% for the AKR. There were significant reductions in MC-caused tumor incidences as a result of beta-NF pretreatment for: sarcomas, lymphomas, and forestomach and skin tumors for the C57BL/6 mice; sarcomas, mesotheliomas, and mammary carcinomas for the C3H mice; mesotheliomas for the BALB/c mice; sarcomas and tumors of the skin, forestomach, and lung for the Swiss mice; and lymphomas for the DBA/2 mice. beta-NF pretreatment did not cause an increase in the incidence of any type of tumor. These results are consistent with the conclusion that inducers of mixed function oxygenase activity generally provide protection against tumorigenesis by systemically administered polycyclic aromatic hydrocarbon carcinogens, probably by increasing rate of detoxification.