Combined and individual effects of isoniazid and thiacetazone on human lymphocyte chromosomes in vitro and in vivo.

Abstract

Genetic effects of the drugs, isoniazid and thiacetazone used for antituberculosis chemotherapy were investigated on human lymphocyte chromosomes in vitro and in vivo. Therapeutic concentrations of these drugs did not induce chromosome aberrations in vitro both in combination and individually during any of the treatment period in 72 h lymphocyte cultures. At higher concentrations both the drugs were found to be cytotoxic. The frequency of chromosome damage was increased significantly in first-division metaphases of the patients, i.e. in vivo during treatment with isoniazid (300 mg) + thiacetazone (150 mg); this could be due to the synergistic action between the metabolites of the two drugs in the body or due to the metabolites of thiacetazone since isoniazid was found to be nonclastogenic in vivo. The frequency of sister chromatid exchanges was not increased in any of the patients except in one, who probably had a higher baseline level. These results suggest that chromosome aberrations and sister chromatid exchanges represent two different lesions. Chromosome damage induced by drugs could lead to congenital malformations, cancer, ageing and therefore contributes to the overall toxicology of the drugs and hazard to human genetic health. Hence drugs like isoniazid and thiacetazone which induce chromosome damage, should be used with caution.