title: DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyrene.
abstract: Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by (32)P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair deficient (Xpc(-/-)) mice were used to study the contribution of nucleotide excision repair in DNA damage removal. DNA adducts were detectable with highest levels in lung followed by sperm and testis. Maximum adduct levels in the lung and testis were observed at Day 1 after exposure, while adduct levels in sperm reached maximum levels at approximately 1 week after exposure. Lung tissue and testis of Xpc(-/-) mice contained significantly higher DNA adduct levels compared to wild type (Wt) mice over the entire 42 day observation period (P < 0.05). Differences in adduct half-life between Xpc(-/-) and Wt mice were only observed in testis. In sperm, DNA adduct levels were significantly higher in Xpc(-/-) mice than in Wt mice only at Day 42 after exposure (P = 0.01). These results indicate that spermatogonia and testes are susceptible for the induction of DNA damage and rely on nucleotide excision repair for maintaining their genetic integrity.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Verhofstad
authors.forename: Conny Th M
authors.initials: CT
authors.lastname: van Oostrom
authors.forename: Jan
authors.initials: J
authors.lastname: van Benthem
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency; D016678:Genome / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice / Q000235:genetics; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D018812:Paternal Exposure; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D009153:Mutagens; C501002:Xpc protein, mouse; D001564:Benzo(a)pyrene