The effect of chlorpromazine and haloperidol on DNA transcription.
The ability of human cells to repair DNA damage can be indirectly assessed by measuring transcriptional activity relating to active genes, a process referred to as RNA synthesis. This study was carried out to investigate the effects of chlorpromazine and haloperidol on the transcriptional activity of actively transcribed genes as an expression of DNA damage and repair. Three cultured human fibroblast lines were used: two were "normal" in previous RNA recovery testings and one was abnormally sensitive to UV irradiation. In the "normal" line, recovery of RNA synthesis occurred within 1 hour of UV after exposure to three concentrations of chlorpromazine (125, 250 and 500 ng/ml) and haloperidol (5, 10 and 20 ng/ml). Following treatment with the same concentrations of chlorpromazine and haloperidol, the UV-sensitive cell line showed markedly depressed recovery of RNA synthesis at 1 and 4 hours. Complete recovery was not reached even after 24 hours. Our results suggest that neuroleptics widely used in clinical practice adversely affect cell lines that are sensitive to DNA-damaging agents.
Barak
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Y
Abarbanel Mental Health Center, Bat Yam, Israel.
Ron
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IG
Sirota
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P
Sobe
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T
Slor
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H
D014150:Antipsychotic Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology*; D004249:DNA Damage; D011088:DNA Ligases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D012313:RNA / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
D014150:Antipsychotic Agents; D012313:RNA; D011088:DNA Ligases; D006220:Haloperidol; D002746:Chlorpromazine