title: Modulation of benzo[a]pyrene-induced covalent DNA modifications in adult and fetal mouse tissues by gestation stage.
abstract: In these studies, we investigated the influence of gestation age on the induction of covalent DNA modifications by benzo[a]pyrene (B[a]P). Timed-pregnant ICR mice were given a single treatment of B[a]P (80 mg/kg, p.o.) on different days of gestation, killed 24 h later and analyzed for the presence of B[a]P-induced DNA adducts using the P1 nuclease version of the 32P-postlabeling method. Our results showed that B[a]P bound to embryonic, placental, fetal and maternal DNA throughout gestation with gestation-stage dependency. Overall, B[a]P bound less to maternal DNA during organogenesis and placentation compared to other stages of gestation and to the non-pregnant stage. The ontogenesis of B[a]P-induced DNA adducts in fetal tissues exhibited organ specificity that had two different types of profiles. With advancing gestation age, one type (lung, carcass and placenta) exhibited a steady linear increase, and the other type [gastrointestinal tract (GIT) and skin] a biphasic increase. In the fetal and maternal organs, adduct levels peaked 2 days before parturition. Over the course of gestation, fetal adduct levels were 70-100% of adult levels in the skin, 7-12% in the GIT, 25-40% in the liver and 15-80% in the lung. The adduct levels in many fetal organs exhibited little relationship to placental adduct levels throughout gestation. Collectively, our results indicate that: (i) transplacental DNA damage induced by B[a]P is determined mainly by fetal competence in metabolic activation and/or detoxification of B[a]P; and (ii) events occurring during placentation and organogenesis inhibit B[a]P binding to maternal tissues.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
authors.forename: L J
authors.initials: LJ
authors.lastname: Lu
authors.forename: M Y
authors.initials: MY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*
chemical_list: D001564:Benzo(a)pyrene; D004247:DNA