Summary
Human lymphocyte cultures from 55 schizophrenic subjects and one manic-depressive subject being treated with the phenothiazine derivative perazine and with other drugs were analyzed with respect to chromosomal damage. The frequency of exchange-type aberrations in these subjects was more than double that in clinically normal control subjects. No correlation was detectable between the aberration frequency and sex, age, smoking and drinking habits, and treatment conditions. It is possible that the elevation of the chromosomal aberration frequency is due to perazine.
In vitro studies with perazine and two main metabolites (desmethylperazine and perazine sulfoxide) with human lymphocytes and CHO cells with and without metabolic activation by liver microsomes gave negative results with respect to the induction of sister chromatid exchanges. Possible differences in the metabolism of perazine in vivo and in vitro are discussed.
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References
Abdullah, S., Miller, O. J.: Effect of drugs on nucleic acid synthesis and cell division in vitro. Dis. Nerv. Syst. 29, 829–833 (1968)
Breyer, U.: Urinary metabolites of 10(3′-(4′'-methylpiperazinyl)-propyl)-phenothiazine (perazine) in psychiatric patients. Biochem. Pharmacol. 18, 777–788 (1968)
Breyer, U.: Metabolism of the phenothiazine drug perazine by liver and lung microsomes from various species. Biochem. Pharmacol. 20, 3341–3351 (1971)
Breyer, U.:Accumulation and elimination of a novel metabolite during chronic administration of the phenothiazine drug perazine to rats. Biochem. Pharmacol. 21, 1419–1429 (1972)
Bridges, B. A., Clemmesen, B. A., Sugimura, T.: Cigarette smoking—does it carry a genetic risk? (ICPEMC publication No. 3.). Mutat. Rev. 65, 71–81 (1979)
Carr, C. R.: The relevance of phenothiazine drug metabolism to pharmacologic and toxic effects. Agressologie 9, 249–257 (1968)
Cohen, M. M., Hirschhorn, K., Frosch, W. A.: In vivo and in vitro chromosomal damage induced by LSD-25. N. Engl. J. Med. 277, 1043–1049 (1967)
Cohen, M. M., Hirschhorn, K., Frosch, W. A.: Cytogenetic effects of tranquilizing drugs in vivo and in vitro. JAMA 207, 2425–2426 (1969)
Cohen, M. M., Lieber, E., Schwartz, H. N.: In vivo cytogenetic effects of perphenazine and chlorpromazine: A negative study. Br. Med. J. 1972 III, 21–23
Gilmour, D. G., Bloom, A. D., Lele, K. P., Robbins, E. S., Maximilian, C.: Chromosomal aberrations in users of psychoactive drugs. Arch. Gen. Psychiatry 24, 268–272 (1971)
Jenkins, E. C.: Phenothiazines and chromosomal damage. Cytologia (Tokyo) 35, 552–560 (1970)
Jose, J. G.: Photomutagenesis by chlorinated phenothiazine tranquilizers. Proc. Natl. Acad. Sci. USA 76, 469–472 (1979)
Kamada, N., Brecher, G., Tjio, J.-H.: In vitro effects of chlorpromazine and meprobamate on blast transformation and chromosomes (35229). Proc. Soc. Exp. Biol. Med. 136, 210–214 (1971)
Kelly-Gravert, F., Legator, M. S.: Photoactivation of chlorpromazine: cytogenetic and mutagenic effects. Mutat. Res. 21, 101–105 (1973)
Korenberg, J. R., Freedlender, E. F.: Giemsa technique for the detection of sister chromatid exchanges. Chromosoma 48, 355–360 (1974)
Lehmann, H. E.: Psychopharmacological treatment of schizophrenia. Schizophr. Bull. 13, 27–45 (1975)
Lewis, A. J. (ed.): Modern drug encyclopedia New York: Yorke Medical Group 1970
Madle, S., Obe, G.: In vitro testing of an indirect mutagen (cyclophosphamide) with human leukocyte cultures: Activation with liver microsomes and use of a dialysis bag. Mutat. Res. 56, 101–104 (1977)
Madle, S., Obe, G.: Testing in vitro of an indirect mutagen (cyclophosphamide) with human leukocyte cultures. Activation by liver perfusion and by incubaction with crude liver homogenate. Mutat. Res. 54, 95–99 (1978)
Matsuyama, S. S., Jarvik, L. F.: Cytogenetic effects of psychoactive drugs. In: Genetics and Psychopharmacology. Mod. Probl. Pharmacopsychiatry 10, 99–132 (1975)
Nielsen, J., Friedrich, U., Tsuboi, T.: Chromosome abnormalities in patients treated with chloropromazine, perphenazine, and lysergide. Br. Med. J. 1969 III, 634–636
Obe, G.: Mutagenicity of alcohol and tobacco smoke. In: Research advances in alcohol and drug problems, Vol. 6, Israel, Y., Glaser, F. B., Kalant, H., Popham, R. E., Schmidt, W., Smart, R. G. (eds.) New York: Plenum (in press) 1980
Obe, G., Herha, J.: Chromosomal damage in chronic alcohol users. Humangenetik 29, 191–200 (1975)
Obe, G., Herha, J.: Chromosomal aberrations in heavy smokers. Hum. Genet. 41, 259–263 (1978)
Obe, G., Ristow, H.: Mutagenic, cancerogenic and teratogenic effects of alcohol. Mutat. Res. 65, 229–259 (1979)
Ohnishi, S., McConnel, H. M.: Interaction of the radical ion of chlorpromazine with deoxyribonucleic acid. J. Am. Chem. Soc. 87, 2293 (1965)
Perry, P., Wolff, S.: New Giemsa method for the differential staining of sister chromatids. Nature 251, 156–158 (1974)
Peterson, K. W., Legator, M. S.: Dominant-lethal effects of triflupromazine in hybrid C3 D2 F1/J mice. Mutat. Res 17, 87–92 (1973)
Pietzcker, A., Müller-Oerlinghausen, B., Schley, J., Chaskel, R., Poppenberg, A., Urban, R.: Beziehungen zwischen Serumkonzentration und klinischen Befunden bei langfristig mit Perazin behandelten schizophrenen Patienten. Arzneim. Forsch. 28, 1302–1303 (1978)
Ray, V. A., Holden, J. H. E., Ellis, J. H., Hyneck, M. L.: A study of triflupromazine in dominant-lethal, cytogenetic and hostmediated assay. Mutat. Res. 18, 301–309 (1973)
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Madle, S., Obe, G., Schroeter, H. et al. Possible mutagenicity of the psychoactive phenothiazine derivative perazine in vivo and in vitro. Hum Genet 53, 357–361 (1980). https://doi.org/10.1007/BF00287056
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DOI: https://doi.org/10.1007/BF00287056