title: Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development.
abstract: Exposure of males to some genotoxic chemicals causes DNA damage in spermatozoa resulting in embryotoxicity and developmental defects in their offspring. This study demonstrates that cisplatin-DNA adducts could be measured in spermatozoa following treatment with the antineoplastic drug, cisplatin. The formation of spermatozoa cisplatin-DNA adducts showed dose and time-dependent increases both in vitro, and in vivo up to 168 h (7 days) after dosing. Treatment of rats with 10 mg cisplatin/kg resulted in spermatozoa Pt-GG adduct levels of approximately 1.0 fmol/microg DNA. When cisplatin-treated male rats were bred to untreated females 6-24 h after cisplatin administration, no adverse developmental effects or decreases in body weight were seen in the offspring although there was a trend towards increased early embryo mortality.
authors.affiliation: TNO Nutrition and Food Research Institute, Toxicology Division, Zeist, The Netherlands. hooser@addl.purdue.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Hooser
authors.forename: W C
authors.initials: WC
authors.lastname: van Dijk-Knijnenburg
authors.forename: I D
authors.initials: ID
authors.lastname: Waalkens-Berendsen
authors.forename: A E
authors.initials: AE
authors.lastname: Smits-van Prooije
authors.forename: N J
authors.initials: NJ
authors.lastname: Snoeij
authors.forename: R A
authors.initials: RA
authors.lastname: Baan
authors.forename: A M
authors.initials: AM
authors.lastname: Fichtinger-Schepman
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism* / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
chemical_list: D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D002945:Cisplatin