Carcinogenesis in Swiss mice by isonicotinic acid hydrazide.

There have been several demonstrations of the limited tumorigenicity of INH in mice. The 1st such experiment was re ported by Juhász et al. (3, 4), who reported the induction of pulmonary adenomas, lymphomas, and leukemia.s in randomly bred mice injected i.p. with INH. In a subsequent study these same investigators found only an induction in lymphomas and leukemias but reported the occurrence of only 1 pulmonary adenoma (5). Other workers have reported on the induction of pulmonary adenomas (1, 7, 8, 10, 11) and it has more recently been suggested that this action may be mediated through hypo thetical metabolism of INH to hydrazine sulfate, which has also been shown to induce lung adenomas (2) in BALB/c mice. In 1 study in the rat (9) no tumors were induced with repeated injec tions of INH and, in fact, in another study in this species the production of hepatomas by p-dimethylaminoazobenzene was inhibited by combined administration of this carcinogen with INH (6). The clinical implications of these various findings have been discussed and many divergent viewpoints presented. The present study has been undertaken because of the clinical interest in this situation. Prior studies reported were terminated before the end of the life-span of the mice. It was felt that addi tional information might be obtained if the experiments were allowed to run to their conclusion.