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. 1979 Jan;76(1):469–472. doi: 10.1073/pnas.76.1.469

Photomutagenesis by chlorinated phenothiazine tranquilizers.

J G Jose
PMCID: PMC382962  PMID: 34152

Abstract

Phenothiazine tranquilizers are widely used pharmaceuticals that have been associated with side effects, such as formation of cataracts, that seem related to light exposure. Because patients may use them over extensive time periods, it is important to determine what deleterious cellular effects these drugs may cause and, if possible, to select or design drugs that do not cause such effects. The results reported here demonstrate that chlorinated phenothiazine drugs can be photoactivated to mutagenic species, whereas the nonchlorinated analogues do not possess this characteristic. None of the phenothiazines tested is mutagenic in the dark. Mutagenicity was observed only in strains of Salmonella typhimurium that lacked excision repair of DNA, and the mutagenicity was elevated in strains that contained the plasmid pKM101, which may enhance error-prone repair.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Lee F. D., Durston W. E. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci U S A. 1973 Mar;70(3):782–786. doi: 10.1073/pnas.70.3.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  3. Copeland E. S., Alving C. R., Grenan M. M. Light-induced leakage of spin label marker from liposomes in the presence of phototoxic phenothiazines. Photochem Photobiol. 1976 Jul;24(1):41–48. doi: 10.1111/j.1751-1097.1976.tb06795.x. [DOI] [PubMed] [Google Scholar]
  4. Corbett M. F., Davis A., Magnus I. A. Personnel radiation dosimetry in drug photosensitivity: field study of patients on phenothiazine therapy. Br J Dermatol. 1978 Jan;98(1):39–46. doi: 10.1111/j.1365-2133.1978.tb07331.x. [DOI] [PubMed] [Google Scholar]
  5. Day R. S., 3rd, Dimattina M. Photodynamic action of chlorpromazine on adenovirus 5:repairable damage and single strand breaks. Chem Biol Interact. 1977 Apr;17(1):89–97. doi: 10.1016/0009-2797(77)90074-6. [DOI] [PubMed] [Google Scholar]
  6. Epstein S. Chlorpromazine photosensitivity. Phototoxic and photoallergic reactions. Arch Dermatol. 1968 Oct;98(4):354–363. doi: 10.1001/archderm.98.4.354. [DOI] [PubMed] [Google Scholar]
  7. Huang C. L., Sands F. L. Effect of ultraviolet irradiation on chlorpromazine. II. Anaerobic condition. J Pharm Sci. 1967 Feb;56(2):259–264. doi: 10.1002/jps.2600560223. [DOI] [PubMed] [Google Scholar]
  8. Imray F. P., MacPhee D. G. Induction of base-pair substitution and frameshift mutations in wild-type and repair-deficient strains of Salmonella typhimurium by the photodynamic action of methylene blue. Mutat Res. 1975 Mar;27(3):299–306. doi: 10.1016/0027-5107(75)90286-9. [DOI] [PubMed] [Google Scholar]
  9. Ippen H., Hofmann N. Doppelte Photoallergisierung gegen Chlorpromazin und Triflupromazin. Berufsdermatosen. 1966 Jun;14(3):159–164. [PubMed] [Google Scholar]
  10. Isono K., Yourno J. Chemical carcinogens as frameshift mutagens: Salmonella DNA sequence sensitive to mutagenesis by polycyclic carcinogens. Proc Natl Acad Sci U S A. 1974 May;71(5):1612–1617. doi: 10.1073/pnas.71.5.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jose J. G., Yielding K. L. Photosensitive cataractogens, chlorpromazine and methoxypsoralen, cause DNA repair synthesis in lens epithelial cells. Invest Ophthalmol Vis Sci. 1978 Jul;17(7):687–691. [PubMed] [Google Scholar]
  12. Kelly-Garvert F., Legator M. S. Photoactivation of chlorpromazine: cytogenetic and mutagenic effects. Mutat Res. 1973 Apr;21(2):101–105. [PubMed] [Google Scholar]
  13. Ljunggren B., Möller H. Phenothiazine phototoxicity: an experimental study on chlorpromazine and its metabolites. J Invest Dermatol. 1977 May;68(5):313–317. doi: 10.1111/1523-1747.ep12494582. [DOI] [PubMed] [Google Scholar]
  14. Ljunggren B., Möller H. Phenothiazine phototoxicity: an experimental study on chlorpromazine and related tricyclic drugs. Acta Derm Venereol. 1977;57(4):325–329. [PubMed] [Google Scholar]
  15. MacPhee D. G., Imray F. P. Mutagenesis by photoactivation of chlorpromazine, a tranquilizer of the phenothiazine group. Aust J Biol Sci. 1974 Apr;27(2):231–234. doi: 10.1071/bi9740231. [DOI] [PubMed] [Google Scholar]
  16. McCann J., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci U S A. 1976 Mar;73(3):950–954. doi: 10.1073/pnas.73.3.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McCann J., Spingarn N. E., Kobori J., Ames B. N. Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A. 1975 Mar;72(3):979–983. doi: 10.1073/pnas.72.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moore D. E. Photosensitization by drugs. J Pharm Sci. 1977 Sep;66(9):1282–1284. doi: 10.1002/jps.2600660919. [DOI] [PubMed] [Google Scholar]
  19. OHNISHI S. I., MCCONNELL H. M. INTERACTION OF THE RADICAL ION OF CHLORPROMAZINE WITH DEOXYRIBONUCLEIC ACID. J Am Chem Soc. 1965 May 20;87:2293–2293. doi: 10.1021/ja01088a040. [DOI] [PubMed] [Google Scholar]
  20. SIMON M. I., VANVUNAKIS H. THE DYE-SENSITIZED PHOTOOXIDATION OF PURINE AND PYRIMIDINE DERIVATIVES. Arch Biochem Biophys. 1964 Apr;105:197–206. doi: 10.1016/0003-9861(64)90253-x. [DOI] [PubMed] [Google Scholar]
  21. Setogawa T., Tamai A., Matsuura H., Ogura C. Lens changes associated with long-term psychotropica therapy. Yonago Acta Med. 1975 Aug;19(2):103–109. [PubMed] [Google Scholar]
  22. Siddall J. R. Phenothiazines in ophthalmology. Int Ophthalmol Clin. 1967 Spring;7(1):207–215. [PubMed] [Google Scholar]
  23. Villarruel M. D., de Toranzo E. G., Castro J. A. Carbon tetrachloride activation, lipid peroxidation, and the mixed function oxygenase activity of various rat tissues. Toxicol Appl Pharmacol. 1977 Aug;41(2):337–344. doi: 10.1016/0041-008x(77)90034-5. [DOI] [PubMed] [Google Scholar]
  24. Walker G. C. Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12. Mol Gen Genet. 1977 Mar 28;152(1):93–103. doi: 10.1007/BF00264945. [DOI] [PubMed] [Google Scholar]
  25. Yoshikawa K., Kurata H., Iwahara S., Kada T. Photodynamic action of fluorescein dyes in DNA-damage and in vitro inactivation of transforming DNA in bacteria. Mutat Res. 1978 Jan;56(3):359–362. doi: 10.1016/0027-5107(78)90205-1. [DOI] [PubMed] [Google Scholar]

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