Naganuma A, Satoh M, Imura N
Cancer Res. 1987 Feb 15;47(4):983-7.
The participation of renal metallothionein (MT) in the toxicity and antitumor activity of cis-diamminedichloroplatinum(II) (cis-DDP) in male mice was examined. Preinduction of MT in the kidney by the s.c. administration of bismuth compounds decreased the lethality and renal and gastrointestinal toxicity caused by a single s.c. injection of cis-DDP. In the present study a correlation between the protective effect of pretreatment with bismuth nitrate against cis-DDP toxicity and the preinduced MT levels in the kidney was observed. Bismuth nitrate pretreatment showed no effect on the antitumor activity of cis-DDP against several transplantable tumors, probably because it induces MT in the kidney but not in tumor tissues. The fact that p.o. preadministration of bismuth subnitrate, an antidiarrheal drug, also depressed the lethal toxicity of cis-DDP is promising for its prompt application in medical attention. Thus, bismuth pretreatment allows higher doses of cis-DDP with no apparent toxicity, resulting in more efficient utilization of this anticancer drug.
研究了肾金属硫蛋白（MT）在顺二氯二氨铂（II）（顺铂）对雄性小鼠的毒性和抗肿瘤活性中的作用。通过皮下注射铋化合物预先诱导肾脏中的MT，可降低单次皮下注射顺铂所引起的致死率以及肾脏和胃肠道毒性。在本研究中，观察到用硝酸铋预处理对顺铂毒性的保护作用与肾脏中预先诱导的MT水平之间存在相关性。硝酸铋预处理对顺铂对几种可移植肿瘤的抗肿瘤活性没有影响，这可能是因为它在肾脏中诱导MT，但在肿瘤组织中不诱导。止泻药次硝酸铋口服预先给药也能降低顺铂的致死毒性，这一事实有望使其在医疗中迅速得到应用。因此，铋预处理允许使用更高剂量的顺铂且无明显毒性，从而更有效地利用这种抗癌药物。
