title: Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumor cells.
abstract: To improve the efficacy of thermochemotherapy we have investigated the individual and combined effects of hyperthermia (44 degrees C) and the calmodulin inhibitor trifluoperazine (30 micrograms/ml) on early plateau phase cultures of mouse EMT6 cells for simultaneous exposures to bleomycin. We found that a non-toxic combination of hyperthermia and trifluoperazine: enhanced the cytotoxicity of bleomycin, increased the frequency of long-lived attachment sites of cellular DNA at the nuclear matrix, and resulted in an accumulation of DNA damage (strand-breaks and alkali-labile lesions) caused by the inhibition of strand-break rejoining and the impaired processing of DNA sites involving base loss. Our findings implicate a role for calmodulin in the control of chromatin structural changes during DNA repair and the study provides a rational basis for the use of calmodulin inhibitors in thermochemotherapy.
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004249:DNA Damage; D006358:Hot Temperature; D066298:In Vitro Techniques; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology*; D014268:Trifluoperazine / Q000494:pharmacology*
chemical_list: D002147:Calmodulin; D001761:Bleomycin; D014268:Trifluoperazine