Effect of pretreatment with beta-naphthoflavone on tumorigenesis by N-nitrosoethylurea in five mouse strains

The non-carcinogenic inducer of the Ah locus, beta-naphthoflavone (beta NF), was administered to females of 5 mouse strains at a dose of 150 mg/kg 48 h before treatment with a tumorigenic dose of the direct-acting carcinogen, N-nitrosoethylurea (ENU), once weekly for 4 weeks. The strains used were C57BL/6, C3H/He and NIH Swiss (responsive to Ah locus induction) and AKR and DBA/2 (induction-non-responsive). The ENU caused primary lung tumors in all strains and in some cases smaller numbers of other neoplasms, including lymphomas, sarcomas and hepatocellular tumors. The beta NF pretreatment did not reduce the numbers of any of the tumors, compared with mice given ENU alone. This result is in contrast to previous findings of a strong protective effect of beta NF against tumorigenesis in Ah-responsive strains by the metabolism-dependent carcinogens, benzo[a]pyrene and 3-methylcholanthrene and confirms that this protection is directly related to enzyme induction. beta NF treatment caused a significant doubling in the number of lung tumor bearers among the ENU-exposed C57BL/6 mice but in no other strain, suggesting the possibility of strain-specific tumor promotion.