Reduction in the transplacental carcinogenic effect of methylcholanthrene in mice by prior treatment with beta-naphthoflavone.

ABSTRACT

Conversion of 14C-benzo[alpha]pyrene (BP) to alkali-soluble and water-phase products, as a measure of aryl hydrocarbon metabolism, was assayed on day 18 of gestation in the livers of pregnant C57BL/6 females and their (C57BL/6 x BALB/c)F1 fetuses. BP metabolism was inducible in both maternal and fetal livers by beta-naphthoflavone (beta-NF), injected ip on day 16 of gestation at doses of 25-130 mg/kg. At 25 and 75 mg/kg beta-NF, fetal liver metabolism of BP was induced 1.5- and 4.5-fold, respectively. The corresponding results for maternal liver indicated no effect at 25 mg/kg and 2.6-fold induction at 75 mg/kg. In a complementary carcinogenesis assay, pregnant mothers were injected ip with beta-NF (25 or 75 mg/kg) on day 15 of gestation and 3-methylcholanthrene (MC) (30 or 150 mg/kg) on day 17. Appropriate vehicle-injected control mice were also obtained. The progeny were examined for lung tumors at 28 weeks of age. The average number of lung tumors per mouse caused by 150 mg/kg MC was significantly reduced by prior treatment with beta-NF, to an extent depending on the dose of the inducer. With the 75 mg/kg dose of beta-NF, the incidence of lung tumors was reduced by half. Induction of carcinogen detoxification in maternal, fetal, and/or placental tissue is a possible mechanism by which beta-NF protected against transplacental MC tumorigenesis.