Effect of the pretreatment with disulfiram on the toxicity and antitumor activity of 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea in Sprague--Dawley rats.
Pretreatment with disulfiram (DSF, 1000 mg/kg p.o.) 2 h prior to intraperitoneal injection of 1-(2-hydroxyethyl)3-(2-chloroethyl)-3-nitrosourea (HECNU, NSC 29485) reduced the acute toxicity of HECNU by 50% in Sprague--Dawley rats. Thereafter the effect of this additional treatment on the chemotherapeutic activity of HECNU was investigated. After intraperitoneal transplantation of Yoshida sarcoma ascites cells untreated rats had a median survival time of 8 days. The therapeutic response to a single application of HECNU alone or of DSF followed by HECNU was compared. HECNU was injected intravenously at logarithmically increasing doses from 15 to 61.8 mg/kg. The maximum survival time was increased to about 14 days in rats treated with HECNU. Pretreatment with DSF (1000 mg/kg) resulted in identical or slightly higher life expectancies; it thus reduced the toxic side effects of HECNU without inhibiting its antitumor potency.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D004221:Disulfiram / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009607:Nitrosourea Compounds / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012517:Sarcoma, Yoshida / Q000188:drug therapy
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C013876:elmustine; D004221:Disulfiram