Action of hydrazine drugs in tumor-free and 1,2-dimethylhydrazine-treated male rats.
In order to evaluate possible carcinogenesis, young adult male Sprague-Dawley rats were fed diets of hydralazine, phenelzine, and isoniazid at levels of 0.020-0.035% for 87 weeks. Hydralazine and isoniazid were also tested by the subcutaneous (sc) route at weekly dosages of 17 and 83 mg/kg, respectively, in both intact and partially hepatectomized rats, but many succumbed after 7 to 49 weeks of treatment. Gastrointestinal lesions were absent and, of the miscellaneous changes, sc lesions occurred sporadically among the control and drug-treated groups. As a further criterion, male weanlings were placed on the diets and, starting on day 15, 1,2-dimethylhydrazine (DMH) was injected sc at 9.0 mg/kg once weekly for the first 7 weeks and twice per week for a total of 23 treatments. The rats were killed 22 weeks after the last injection, at which time colon adenocarcinomas were observed in over 80% per group, the total number being significantly greater for the isoniazid group due to heightened tumor occurrence at the distal colon. The tumor number in the descending colon for phenelzine was also increased but the overall score, as with the hydralazine group, was in the range of the DMH injected controls. Small intestinal adenocarcinomas were lower in number and involved fewer rats on the hydralazine and phenelzine diets as compared to the isoniazid and control groups. Based on the current data, it is concluded that on long term exposure of DMH treated rats to the monoamine oxidase inhibitors, hydralazine and phenelzine are not cocarcinogenic, whereas isoniazid enhances colon carcinogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Gershbein
L L
LL
Biochemistry Section, John F. Kennedy Health Care Corporation, Chicago, IL 60634.
Rao
K C
KC
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced*; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004127:Dimethylhydrazines; D006830:Hydralazine / Q000633:toxicity*; D007279:Injections, Subcutaneous; D007538:Isoniazid / Q000633:toxicity*; D008297:Male; D010624:Phenelzine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004127:Dimethylhydrazines; D006830:Hydralazine; D019813:1,2-Dimethylhydrazine; D010624:Phenelzine; D007538:Isoniazid