Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development.
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.
Hooser
S B
SB
TNO Nutrition and Food Research Institute, Toxicology Division, Zeist, The Netherlands. hooser@addl.purdue.edu
van Dijk-Knijnenburg
W C
WC
Waalkens-Berendsen
I D
ID
Smits-van Prooije
A E
AE
Snoeij
N J
NJ
Baan
R A
RA
Fichtinger-Schepman
A M
AM
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*
D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D002945:Cisplatin