Lung tumorigenesis and hyperplasia in offspring associated with the Ahd allele following in utero exposure to 3-methylcholanthrene.
This study was conducted to determine if the Ah genotype could influence the incidence of tumorigenesis in offspring exposed to 3-methylcholanthrene (3-MC) during the fetal period. Male F1 hybrids (Ahb/Ahd) were backcrossed to Ahd/Ahd females, resulting in pregnant mice containing litters with a 1:1 ratio of Ahb/Ahd (AHH-inducible) and Ahd/Ahd (AHH-noninducible) fetuses. Dams were exposed by gavage to corn oil or to 3-MC at 7, 21, or 63 mg/kg on Days 15, 16, and 17 of gestation, or to the positive control urethane at 1 mg/g ip on Day 17. The phenotype of surviving offspring was determined by hepatic aryl hydrocarbon hydroxylase (AHH) activity. The lung was the major site of neoplastic involvement in adult offspring 6 months after in utero exposure to 3-MC. Dose-related responses in all 3-MC treatment groups were obtained for percent nodule-bearing animals, percentage adenoma-bearing animals, mean number of nodules per animal, mean nodular size per animal, and diffuse bronchiolar hyperplasia. Correlation of Ah phenotype with adult tumorigenesis indicated that genetically nonresponsive (Ahd/Ahd) offspring had a higher incidence of nodules, adenomas, and diffuse bronchiolar hyperplasia than responsive offspring within the same treatment group. Thus, when fetuses are exposed in the same maternal environment to 3-MC, genetic differences in Ah genotype may influence susceptibility to transplacental carcinogenesis.
D000483:Alleles; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005838:Genotype; D006965:Hyperplasia / Q000139:chemically induced; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D008431:Maternal-Fetal Exchange; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D011247:Pregnancy
D008748:Methylcholanthrene