Long‐Term (Imprinting) Effects of Transplacental Treatment of Mice with 3‐Methylcholanthrene or β‐Naphthoflavone on Hepatic Metabolism of 3‐Methylcholanthrene

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Abstract
Foetal mice of genotype AhbAhd(responsive to induction of metabolism of polycyclic aromatic hydrocarbons [PAH]) or AhdAhd(non‐responsive) were exposed transplacentally on gestation day 17 to a single dose of 3‐methylcholanth‐rene (MC, 5–17. mg/kg) with or without prior treatment on day 15 with β‐naphthoflavone (βNF, 150 mg/kg). The mothers were themselves either induction‐responsive [(C57BL/6 x DBA/2)F1] or non‐responsive (DBA/2). Metabolism of [14C]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 (AhbAhd) and non‐induced (AhdAhd) individuals, and was significant only when the mother and/or the foetus was inducible. βNF 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.