Toxicology studies with cytembena (NSC-104801), an antineoplastic agent with a multispecies nephrotoxic effect.

Abstract

The toxic effects of cytembena in beagle dogs and rhesus monkeys were investigated with the drug given as single or daily iv injections in doses ranging from 12.5 to 200 mg/kg/day to dogs and 6.25 to 50 mg/kg/day to monkeys. Renal tubular damage was a major drug- and dose-related finding in both species and was clinically indicated by an accompanying uremia, elevated serum creatinine, and proteinuria. In the kidney, the primary lesion was cellular necrosis and desquamation of the distal tubular epithelium in animals given the lowest toxic doses. More severe but similar histologic changes produced by this drug were further characterized by single dose studies in mice which showed renal mitochondrial swelling and disruption plus generalized cell swelling as progressive, subcellular developments which were well established 24 hours after treatment. Cellular regeneration in the renal tubular epithelium was found in dogs and monkeys retained 6 weeks for observation after treatment, although functional recovery was inconsistent. A toxic effect to lymphoid tissue was an additional finding which is described.