Hepatic Carcinogenesis in CBA/Cb/Se Mice and Cb/Se Rats by Isonicotinic Acid Hydrazide and Hydrazine Sulfate

Summary

Isonicotinic acid hydrazide (INH) is widely used in the treatment and prophylaxis of tuberculosis. Hydrazine is its principal metabolite. INH administered in aqueous solution by stomach tube to CBA/Cb/Se mice caused liver tumors in 17% of the males and in 12% of the females and increased lung tumors to 61 and 76%. Oral administration of hydrazine sulfate in aqueous solution increased the liver tumors to 62 and 71% in male and female CBA/Cb/Se mice, respectively, and the number of lung tumors to 76 and 90%. Administration of INH in drinking water induced liver tumors in 2% and lung tumors in 4% of male Cb/Se rats, and breast tumors in 27% of female Cb/Se rats. Hydrazine sulfate administered by stomach tube induced liver tumors in 30% of male Cb/Se rats, and lung tumors in 21 and 27% of male and female Cb/Se rats, respectively. Histologically, the liver tumors in mice were hepatocarcinomas, the lung tumors adenomas and adenocarcinomas; in rats the liver tumors were hepatocarcinomas and spindle cell sarcomas, the lung tumors adenocarcinomas, and the breast tumors fibroadenomas.