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 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-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 [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. 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.
Anderson
L M
LM
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21701.
Jones
A B
AB
Riggs
C W
CW
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008431:Maternal-Fetal Exchange; D008748:Methylcholanthrene / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D011247:Pregnancy; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D001189:Aryl Hydrocarbon Hydroxylases