HEPATIC DRUG-METABOLIZING ENZYME-ACTIVITY AND TUMORIGENESIS IN MICE FOLLOWING PERINATAL EXPOSURE TO BENZO(A)PYRENE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 1  (1) , 85-96
Abstract
In utero exposure to polycyclic aromatic hydrocarbon carcinogens (PAH) results in a high incidence of pulmonary and other tumors in the offspring, usually after a long latency period. The present study tested the hypothesis that perinatal exposure to benzo(a)pyrene (BP) alters microsomal mixed-function oxidase (MFO) activity such that the offspring are more susceptible to tumorigenesis induced by postnatal challenge with a PAH. The question of whether the gestational age at which BP exposure occurred was a determinant of the proposed alterations was studied. Swiss mice were treated with BP on day 3, 8, 10, 12, 14 or 18 of gestation. Subgroups from each gestational-age treatment group and appropriate controls were studied for enzyme activity or were challenged with 3-methylcholanthrene (3-MC) when 3 mo. old. Female offspring of BP-treated mice had significantly elevated hepatic microsomal aminopyrine demethylase activity; cytochrome P-450 concentrations were significantly lower in male offspring. The most striking finding was the increased susceptibility to tumorigenesis of female offspring. Latency for local tumors was decreased by 2 wk; tumors were more frequent and grew more rapidly. Significantly more female offspring had local and pulmonary lesions and the total number of pulmonary adenomas was also significantly higher. Further studies are required to determine if the developmental alterations in hepatic (MFO) activity resulting from perinatal exposure to PAH relate in a causative way to the enhanced susceptibility of female offspring to tumorigenesis.