cis-diamminedichloroplatinum(II)-induced sister-chromatid exchanges and chromosome aberration formation in cultured human lymphocytes and their inhibition by sodium thiosulfate.
cis-Diamminedichloroplatinum(II) (cis-DDP)-induced sister-chromatid exchanges (SCEs) and chromosome aberration formation were studied in human lymphocytes. The mitotic index decreased abruptly at 2 X 10(-6) M cis-DDP and the frequency of SCEs was dose-related; a marked increase was recorded at 10(-6) M cis-DDP. A dose-dependent effect was also found for chromosome aberration formation at concentrations between 10(-11) and 4 X 10(-6) M. The aberrations observed were primarily chromatid breaks and gaps. We also examined the inhibition of these genotoxicities by treating the cells with sodium thiosulfate (STS). Simultaneous treatment with 10(-4)-10(-3) M STS (100-1000-fold molar ratio to cis-DDP) significantly reduced the frequency of SCEs induced by 10(-6) M cis-DDP. Furthermore, a 3-h delay in treating with STS significantly reduced cis-DDP-induced SCEs, but not chromosome aberration formation.
Ohe
T
T
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Tsuda
S
S
Sakata
Y
Y
Taniwaki
M
M
Misawa
S
S
Abe
T
T
D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008940:Mitotic Index; D012854:Sister Chromatid Exchange; D013885:Thiosulfates / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin