The effect of trifluoperazine on the genotoxicity of bleomycin in cultured human lymphocytes

The effects of trifluoperazine on the toxicity and mutagenicity of bleomycin were examined in cultured human lymphocytes. Lymphocyte cultures were initiated from three adult healthy non-smoking male volunteers. Cultures were exposed to the drugs for either three or twenty hours prior to cell collection. The toxic and clastogenic effects of the different treatments were represented by the reduction in the mitotic indices and the induction of chromosomal aberrations (CA) respectively. Both TFP and BLM significantly increased CA frequencies and reduced the mitotic indices (MI) following all treatments. The reduction in the mitotic indices and the increase in CA frequencies induced by the combined administration of both BLM and TFP were highly significant (p ≤ 0.001), but they were not significantly different from the sum of those induced by the separate treatments with the two drugs. These combined treatments, however, potentiated the odds ratios 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 compared to those of the separate treatments suggested a significant enhancement in the expected chemotherapeutic effects of BLM when administered with TFP.