LONG-TERM (IMPRINTING) EFFECTS OF TRANSPLACENTAL TREATMENT OF MICE WITH 3-METHYLCHOLANTHRENE OR BETA-NAPHTHOFLAVONE ON HEPATIC-METABOLISM OF 3-METHYLCHOLANTHRENE

Foetal mice of genotype Ah(b)Ah(d) (responsive to induction of metabolism of polycyclic aromatic hydrocarbons [PAH]) or Ah(d)Ah(d) (non-responsive) were exposed transplacentally on gestation day 17 to a single dose of 3-methylcholanthrene (MC, 5-175 mg/kg) with or without prior treatment on day 15 with beta-naphthoflavone (beta-NF, 150 mg/kg). The mothers were themselves either induction-responsive [(C57BL/6 x DBA/2)F1] or non-responsive (DBA/2). Metabolism of [C-14]MC by homogenates of livers from the transplacentally-exposed offspring was quantified at 9 months of age (first experiment) or 13 months (second experiment) with or without prior inducing treatment with MC. The foetal exposure to MC had a permanent effect on MC metabolism by the adult hepatic homogenates in both experiments. In most instances the effect was positive in direction and small in magnitude (15-30%). It was dose-dependent with regard to transplacental MC, occurred in both induced (Ah(b)Ah(d)) and non-induced (Ah(d)Ah(d)) individuals, and was significant only when the mother and/or the foetus was inducible. Beta-NF itself did not have a positive imprinting effect. In some cases it either reduced or potentiated the long-term imprinting effect of MC, depending on the MC dose and the phenotype of the mother. These results confirm that transplacental exposure to a carcinogenic PAH may permanently alter metabolism of the chemical in later life. and indicate that this imprinting action is dependent on induced metabolism of the chemical in the mother and/or foetus.