Chlorpromazine-induced damage on nucleic acids: a combined cytogenetic and biochemical study.
Chlorpromazine is now emerging as an adjuvant chemotherapeutic agent for the treatment of neoplasia. This was further supported in the present study by the following lines of evidence: it was shown that chlorpromazine causes damage in a series of native nucleic acids, though at somewhat high concentrations. Furthermore, chlorpromazine and caffeine were shown to act synergistically to potentiate the cytogenetic effect of adriamycin on human lymphocytes in vitro and on Ehrlich ascites tumour (EAT) cells in vivo. It is suggested that chlorpromazine alone or in combination with caffeine may exert its cytotoxic effect on normal and neoplastic cells not only indirectly, i.e. by facilitating the intracellular retention of adriamycin, but also directly by intercalating into nucleic acids.
Department of Medical Biology and Genetics, Medical School, Democritean University of Thrace, Alexandroupolis, Greece.
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T
Lialiaris
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Pantazaki
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E
Sivridis
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Mourelatos
D000818:Animals; D010582:Bacteriophage lambda / Q000187:drug effects / Q000235:genetics; D002110:Caffeine / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000633:toxicity*; D004249:DNA Damage; D004279:DNA, Viral / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007364:Intercalating Agents / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008940:Mitotic Index / Q000187:drug effects; D010957:Plasmids / Q000187:drug effects; D012313:RNA / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D007364:Intercalating Agents; D002110:Caffeine; D012313:RNA; D004317:Doxorubicin; D002746:Chlorpromazine