Neonatal toxicity in mice associated with the Ahb allele following transplacental exposure to 3-methylcholanthrene.
This study was conducted to determine if the Ah genotype in mice could influence the incidence of neonatal mortality following maternal exposure to 3-methylcholanthrene (3-MC). Male F1 hybrids (Ahb/Ahd) produced from a cross of C57BL/6J and DBA/2J were backcrossed to DBA/2J females. This backcross mating resulted in noninducible pregnant mice (Ahd/Ahd) containing litters with a 1:1 ratio of AHH-inducible (Ahb/Ahd) and noninducible (Ahd/Ahd) fetuses. Dams were exposed by the oral route to 3-MC in corn oil at doses of 7, 21, or 63 mg/kg/day on Days 15, 16, and 17 of pregnancy, or to the positive control agent urethane at 1 mg/g ip on Day 17. The phenotype of surviving offspring was determined by zoxazolamine paralysis time and hepatic aryl hydrocarbon hydroxylase (AHH) activity measurements. Dose-related responses in all 3-MC treatment groups were obtained in measures of neonatal toxicity, i.e., number of litters surviving to term, litter size at birth, survival to weaning, and weight gain to 13 weeks of age. Correlation of the Ah phenotype with the neonatal toxicity data indicated that genetically responsive offspring had higher levels of neonatal toxicity than nonresponsive offspring within the same exposure groups. Thus, when fetuses are exposed in the same maternal environment to 3-MC, genetic differences in Ah genotype may influence the susceptibility to neonatal toxicity.
D000284:Administration, Oral; D000483:Alleles; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001835:Body Weight; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D008431:Maternal-Fetal Exchange; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D011247:Pregnancy; D015049:Zoxazolamine / Q000378:metabolism
D008748:Methylcholanthrene; D015049:Zoxazolamine; D001189:Aryl Hydrocarbon Hydroxylases