Mutagenic activity of isoniazid in the mouse

Abstract

Isoniazid was tested for genetic activity in the mammalian spot test by treating in utero mouse embryos, derived from the crosses C57 B1/6J X T-stock and NMRI X DBA/2, heterozygous for various loci affecting coat color. Induction of genetic changes is seen by expression of recessive alleles in colored spots within the fur of the adult animal in a non-agouti background. Injecting mothers with isoniazid (100 mg/kg ip), an expression of recessive loci was found in 7.41% of the F1 animals in the cross C57 B1/6J X T-stock, while in the NMRI X DBA/2 cross 2.92% animals with recessive spots were detected. The control frequencies were respectively 0 and 0.78% animals with recessive spots. The positive control substance, ethyl methanesulfonate (100 mg/kg ip), yielded 5.97% and 4.71% animals carrying a recessive spot in the fur, respectively. These studies clearly demonstrate for the first time the induction of genetic damage other than cytological damage in somatic cells of mice by isoniazid.