The effect of trifluoperazine on the genotoxicity of bleomycin in culturedhuman lymphocytes

The effects of trifluoperazine on the toxicity and mutagenicity of bleomyci n were examined in cultured human lymphocytes. Lymphocyte cultures were ini tiated from three adult healthy non-smoking male volunteers. Cultures were exposed to the drugs for either three or twenty hours prior to cell collect ion. The toxic and clastogenic effects of the different treatments were rep resented by the reduction in the mitotic indices and the induction of chrom osomal aberrations (CA) respectively. Both TFP and BLM significantly increa sed CA frequencies and reduced the mitotic indices (MI) following all treat ments. The reduction in the mitotic indices and the increase in CA frequenc ies induced by the combined administration of both BLM and TFP were highly significant (p less than or equal to 0.001), but they were not significantl y different from the sum of those induced by the separate treatments with t he two drugs. These combined treatments, however, potentiated the odds rati os compared to those of the separate drug treatments. Therefore, though the effect of TFP on the clastogenic and cytotoxic effects of BLM was additive , the observed potentiation of the odds ratios of the combined treatments c ompared to those of the separate treatments suggested a significant enhance ment in the expected chemotherapeutic effects of BLM when administered with TFP.