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  • Title: Potentiation of sensitivity to bleomycin and the drug-induced DNA damage in EMT6 cells by the calmodulin inhibitor trifluoperazine.
    Author: Smith PJ, Mircheva JJ, Bleehen NM.
    Journal: Acta Physiol Pharmacol Bulg; 1987; 13(1):41-5. PubMed ID: 2441572.
    Abstract:
    It has been shown that inhibitors of calmodulin can increase the sensitivity of rodent cells to Bleomycin by interfering with DNA repair functions. As a result of this study we have found that treatment of plateau-phase EMT6 cells with Bleomycin causes a decrease in cell survival due to DNA damage. This toxic effect can be potentiated by the addition of a nonlethal dose of the calmodulin inhibitor Trifluoperazine. Furthermore, it was found that Trifluoperazine greatly potentiated Bleomycin-induced DNA breakage. Considering the results obtained by alkaline-denaturation assay (detects single-strand breaks, including these arising from alkali-labile lesions) and nucleoid sedimentation (in neutral sucrose gradients) assay (detects only frank breaks), a difference, presumably due to the Trifluoperazine-produced discrete block in the repair of Bleomycin-induced DNA alkali-labile lesions was found. These data suggest a role for calmodulin in the DNA repair pathway and provide a rational basis for the use of calmodulin inhibitors in cancer chemotherapy.
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