Effect of sulfhydryl-containing compounds on the antitumor effects of adriamycin.

Abstract The lethality of single doses of adriamycin (ADR) in male mice has been reported to be antagonized by concurrent administration of the sulfhydryl compounds cysteamine (CYS) or N -acetylcysteine (NAC). The present investigation was undertaken to determine whether CYS and NAC also have an effect on the antitumor activity of ADR. The life span of male mice bearing a transplantable Ehrlich ascites carcinoma was significantly increased by ADR administered intraperitoneally for 4 successive days at sublethal dosages of 1.5 or 2.5 mg/kg/day. CYS or NAC (50 and 100 mg/kg ip, respectively) administered 1 hr before and 7 hr after ADR treatment did not inhibit the antitumor activity of ADR and further increased the life span of these tumorbearing animals. The uptake of ADR by Ehrlich ascites cells in vitro was not affected by CYS or NAC. ADR-induced inhibition of [ 3 H]thymidine incorporation into DNA of Ehrlich ascites cells in vitro was also not affected by CYS or NAC. The mechanism of sulfhydryl-induced protection against the cardiotoxicity of ADR appears not to interfere with the antitumor activity of ADR.