[Effect of sodium thiosulfate on the antitumor effect and nephrotoxicity of CDDP in human gastric cancer transplanted in nude mice].
Sodium thiosulfate (STS) is known to decrease the nephrotoxicity of cisplatin (CDDP). CDDP has been recognized effective in some type of gastric cancers, and there has been an attempt to examine the optimal dose of STS, which suppresses the CDDP-induced nephrotoxicity without interfering its anticancer effect. The gastric cancer cell lines (KATO-III and MKN 45) were transplanted into BALB/c nu/nu mice. CDDP was injected intraperitoneally once a week 5 times with various doses of STS, and the effects of STS on the antitumor effect as well as the nephrotoxicity of CDDP were examined. The antitumor effect of CDDP (9 mg/kg) was suppressed by 30% with the simultaneous injection of 372 mg/kg (50 fold-molar radio of STS to CDDP) and abolished by 1,488 mg/kg (200 fold-molar radio) of STS. The elevated serum BUN and the kidney content of platinum following CDDP administration were at the normal ranges in the nude mice received these doses of STS. Also, the atrophic and regenerative changes of the kidney tubules induced by CDDP were scarcely observed in these nude mice. From these results, only 50 fold-molar radio of STS to CDDP suppresses the nephrotoxicity of CDDP without interfering its antitumor effect, and this rather smaller amounts of STS is considered to be optimal. Further studies, however, will be needed for clinical application.
Saito
D
D
Dept. of Int. Medicine, National Cancer Center Hospital.
Fujii
T
T
Yoshida
S
S
Ohkura
H
H
Oguro
Y
Y
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013885:Thiosulfates / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000931:Antidotes; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin