title: Spermatogenesis is not impaired in a nucleotide excision repair-deficient min mouse model with or without neonatal mutagen treatment.
abstract: Mice deficient in the xeroderma pigmentosum group A gene (Xpa) exhibit impaired nucleotide excision repair (NER) and are expected to accumulate bulky DNA adducts when subjected to certain compounds (eg, heterocyclic amines). Multiple intestinal neoplasia (Min) mice (B6(Min)(/+)) are particularly sensitive to low concentrations of mutagenic compounds in food. They develop intestinal tumors spontaneously, and the number and size of the tumors increase following exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which humans are exposed to via fried food. We previously reported that NER is inefficient in adult testicular cells. Reduced NER (genetic deficiency; Xpa(-/-)) is expected to represent risk factors for PhIP-induced genotoxicity and could possibly disturb spermatogenesis, particularly in B6(Min)(/+) mice. We therefore studied spermatogenesis in mice with combinations of Xpa and Min or wild-type genotypes 11 weeks after exposure to PhIP on days 3 to 6. Fewer offspring were obtained from B6(Min)(/+)Xpa(-/-) than from B6(Min)(/+)Xpa(+/+) or B6(Min)(/+)Xpa(+/-). Distributions of the different testicular cell types, indicative of normal spermatogenesis and relative testes weights, did not differ significantly in PhIP-exposed or unexposed mice regardless of their genotypes. We conclude that the removal of bulky DNA adducts does not seem to be essential for normal spermatogenesis.
authors.affiliation: Department of Infectious Diseases, Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway. ashild.andreassen@fhi.no
authors.forename: Ashild
authors.initials: A
authors.lastname: Andreassen
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Steffensen
authors.forename: Ann-Karin
authors.initials: AK
authors.lastname: Olsen
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Richard
authors.initials: R
authors.lastname: Wiger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018736:DNA Adducts / Q000235:genetics; D004260:DNA Repair / Q000502:physiology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009153:Mutagens / Q000633:toxicity; D013091:Spermatogenesis / Q000502:physiology*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
chemical_list: D018736:DNA Adducts; D009153:Mutagens; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse