Benzo[a]pyrene-induced DNA damage in mouse fetal tissues.
We have studied the occurrence and persistence of DNA damage in the hepatic and pulmonary tissues of fetal, newborn and adult CD1 mice exposed to selected doses of benzo[a]pyrene (BP) by utilizing the alkaline elution technique. Firstly 12-, 15- and 18-day pregnant and 1-, 7- and 82 to 85-day-old mice were treated i.p. with 10 mg/kg BP and the DNA fragmentation evaluated 4 h later. This approach indicated that, among the ages considered, 15-day-old fetuses were the most sensitive to BP genotoxicity. Therefore we concentrated on this intrauterine stage and evaluated the role of the maternal and fetal environment on the induction and the kinetics of disappearance of DNA damage by BP. BP at the dose levels of 0, 2 and 10 mg/kg was injected i.p. into pregnant females or directly into single fetuses and the fetal livers and lungs recovered 2, 4, 24 and 48 h later. According to the above protocol other 12-day-pregnant mice were treated i.p. with 500 mg/kg arochlor and their 15-day-old fetuses directly injected with the same doses of BP. The results showed that the maximum DNA damage is present at 4 h following BP treatment and it almost disappeared at 48 h irrespective of the route of BP administration. However, the decrease was not uniform and while at 48 h the lesion reached the control level in the liver, it remained slightly higher in the lung. The effects where markedly magnified in the arochlor-induced groups where the intrafetal injection of BP caused an average 2-fold increase and an earlier appearance of DNA damage in both liver and lung compared with uninduced animals. The amplified BP activity induced by arochlor was particularly evident in the lung where at 48 h there was still a significant amount of DNA damage. Since the lung is a preferential site of transplacental carcinogenic effects in CD1 mice, our results favor the conclusion that a correlation exists between DNA damage and tumor induction in the fetuses of this mouse strain.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D004247:DNA; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy
D001564:Benzo(a)pyrene; D004247:DNA