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Toxic and Pathologic Effects of 4,4'-Diacetyl-diphenyl-ureabis(guanylhydrazone), A New Antileukemic Agent¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

The toxic effects of 4,4'-diacetyl-diphenyl-urea-bis(guanyl-hydrazone), a compound with pronounced activity against several mouse leukemias, were studied in mice, rats, rabbits, dogs, and monkeys. In each of these species, i.v. injection of the drug caused acute paralysis leading to apnea and death. In the surviving animals, the acute syndrome was completely reversible within 30 minutes. No cumulative effects occurred in dogs after repeated injection of sublethal paralytic doses. Local cytotoxicity was severe after s.c., i.m., or i.p. doses. Orally, the drug had no effect. Hepatotoxicity occurred in rats, dogs, and monkeys and was the major subacute effect. In these 3 species, acute pulmonary edema and lymphoid depression were also seen. In rats, hypoglycemia occurred terminally after repeated treatments; alopecia and dermatitis also developed. Bone marrow depression was minor.

¹ This investigation was supported in part by research Grant CA-04130 from the National Cancer Institute, USPHS.

Received 8/12/68. Accepted 12/20/68.