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

被引:25
作者
Hooser, SB [1 ]
van Dijk-Knijnenburg, WCM [1 ]
Waalkens-Berendsen, IDH [1 ]
Smits-van Prooije, AE [1 ]
Snoeij, NJ [1 ]
Baan, RA [1 ]
Fichtinger-Schepman, AMJ [1 ]
机构
[1] TNO, Nutr & Food Res Inst, Div Toxicol, NL-3700 AJ Zeist, Netherlands
关键词
cisplatin; DNA adducts; spermatozoa; rats; development; embryotoxicity;
D O I
10.1016/S0304-3835(99)00415-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/mu g 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. All rights reserved.
引用
收藏
页码:71 / 80
页数:10
相关论文
共 39 条
[1]  
BEDFORD P, 1988, CANCER RES, V48, P3019
[2]   Gonadal function of patients treated with cisplatin based chemotherapy for germ cell cancer [J].
Brennemann, W ;
StoffelWagner, B ;
Helmers, A ;
Mezger, J ;
Jager, N ;
Klingmuller, D .
JOURNAL OF UROLOGY, 1997, 158 (03) :844-850
[4]   MALE MEDIATED TERATOGENESIS [J].
COLIE, CF .
REPRODUCTIVE TOXICOLOGY, 1993, 7 (01) :3-9
[5]  
DIWAN BA, 1993, CANCER RES, V53, P3874
[6]  
DIXON RL, 1980, FED PROC, V39, P66
[7]  
Eddy E. M., 1989, TOXICOLOGY MALE FEMA, P31
[9]  
FICHTINGERSCHEP.AM, 1982, NUCLEIC ACIDS RES, V10, P5245
[10]  
FICHTINGERSCHEPMAN AMJ, 1987, CANCER RES, V47, P3000