title: Environmental exposure of the mouse germ line: DNA adducts in spermatozoa and formation of de novo mutations during spermatogenesis.
abstract: BACKGROUND
  Spermatozoal DNA damage is associated with poor sperm quality, disturbed embryonic development and early embryonic loss, and some genetic diseases originate from paternal de novo mutations. We previously reported poor repair of bulky DNA-lesions in rodent testicular cells.
  
  
  RESULTS
  We studied the fate of DNA lesions in the male germ line. B[a]PDE-N(2)-dG adducts were determined by liquid chromatography-tandem mass spectrometry, and de novo mutations were measured in the cII-transgene, in Big Blue mice exposed to benzo[a]pyrene (B[a]P; 3 x 50 mg/kg bw, i.p.). Spermatozoa were harvested at various time-points following exposure, to study the consequences of exposure during the different stages of spermatogenesis. B[a]PDE-N(2)-dG adducts induced by exposure of spermatocytes or later stages of spermatogenesis persisted at high levels in the resulting spermatozoa. Spermatozoa originating from exposed spermatogonia did not contain DNA adducts; however de novo mutations had been induced (p = 0.029), specifically GC-TA transversions, characteristic of B[a]P mutagenesis. Moreover, a specific spectrum of spontaneous mutations was consistently observed in spermatozoa.
  
  
  CONCLUSIONS
  A temporal pattern of genotoxic consequences following exposure was identified, with an initial increase in DNA adduct levels in spermatozoa, believed to influence fertility, followed by induction of germ line de novo mutations with possible consequences for the offspring.
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. ann.karin.olsen@fhi.no
authors.forename: Ann-Karin
authors.initials: AK
authors.lastname: Olsen
authors.forename: Ashild
authors.initials: A
authors.lastname: Andreassen
authors.forename: Rajinder
authors.initials: R
authors.lastname: Singh
authors.forename: Richard
authors.initials: R
authors.lastname: Wiger
authors.forename: Nur
authors.initials: N
authors.lastname: Duale
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene; D002853:Chromatography, Liquid; D018736:DNA Adducts; D004781:Environmental Exposure; D005854:Germ Cells; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013091:Spermatogenesis; D053719:Tandem Mass Spectrometry
chemical_list: D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene