Improved therapeutic index of cis-diammine dichloro platinum by diethyldithiocarbamate in rodents.
cis-Diammine Dichloro Platinum (DDP) is an effective antitumor agent. However, nephrotoxicity remains a major dose limiting factor in its clinical application. The present experiments with Fischer 344 rats showed that diethyldithiocarbamate, an alkyl dithiocarbamate, prevents DDP induced acute nephrotoxicity, and increases the LD50 from 8.3 to 10.8 mg/kg. The subacute DDP toxicity was also prevented by the DTC in B6D2F1/J mice. Further, studies with L1210 Leukemic mice indicate that DTC in dosages up to 250 mg/kg did not interfere with the antitumor effects of DDP. The present experiments, therefore, add evidence to the thesis that thiol compounds may "selectively" protect normal tissues against agents which form interstrand or intrastrand cross links with DNA. Thiol compounds, therefore, may have a wider clinical application in patients receiving cancer chemotherapy.
D000818:Animals; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects; D007928:Lethal Dose 50; D007938:Leukemia / Q000401:mortality; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology*
D013859:Thiocarbamates; D004050:Ditiocarb; D002945:Cisplatin