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Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development

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Author: Hooser, S.T. · Dijk-Knijnenburg, C.M. van · Waalkens-Berendsen, I.D.H. · Smits-van Prooije, A.E. · Snoeij, N.J. · Baan, R.A. · Fichtinger-Schepman, M.J.
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Cancer Letters, 1, 151, 71-80
Identifier: 58491
doi: doi:10.1016/S0304-3835(99)00415-2
Keywords: Nutrition · Cisplatin · Development · DNA adducts · Embryotoxicity · Rats · Spermatozoa · Cisplatin · Animal cell · Antibody specificity · Carcinogenesis · Cell killing · Cross linking · DNA adduct · DNA binding · DNA damage · Embryotoxicity · Fetus development · Infertility · Nonhuman · Priority journal · Rat · Spermatogenesis · Spermatozoon · Animals · Body Weight · Cisplatin · DNA Adducts · DNA Damage · Embryonic and Fetal Development · Female · Fetal Death · Male · Pregnancy · Rats · Rats, Wistar · Spermatozoa · Animalia


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/μg 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. (C) 2000 Elsevier Science Ireland Ltd. Chemicals/CAS: Cisplatin, 15663-27-1; cisplatin-DNA adduct; DNA Adducts