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Pharmacology of Mitomycin C

I. Toxicity and Pathologic Effects^*

( Pharmacology Section, Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N.Y.)

The toxicity of mitomycin C has been studied in mice, rats, cats, dogs, and rhesus monkeys. Fatal poisoning was uniformly protracted in all five species. Its features were anorexia, steady losses in weight, emesis (in cats and dogs), diarrhea, dehydration, and delayed deaths. Fevers were common in dogs.

The agent had notable hematologic effects. In dogs these included reticulocytopenia, leukopenia, and decreased numbers of nucleated cells in bone marrow aspirates.

Hypoplasia of bone marrow, lymphoid tissue damage, and lesions in intestinal epithelium were common pathologic effects in dogs, rats, and monkeys. There were additional lesions: widespread hemorrhages in dogs and monkeys, damage of the epithelium of the glandular stomach in rats, necrotizing nephrosis in monkeys, and liver damage in dogs. Intraperitoneal injections had a direct toxic effect on the peritoneum of rats.

These studies suggest that suppression of hematopoiesis and intestinal injury account for the lethal effects of mitomycin C. The close association of lesions in normal, proliferating tissues with antitumor effects is a pharmacologic property shared by most known chemotherapeutic agents.

^* Aided by Grant CY 3192 and CCNSC Contract No. SA-43-ph-2445 from the National Cancer Institute, U.S.P.H.S., and by funds from the Max E. Fleischmann Foundation of Nevada and the Elsa U. Pardee Foundation. A preliminary account of this work has already appeared (16).

Received 4/11/60.

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