Irreversible binding of the chloropromazine radical cation and of photoactivated chlorpromazine to biological macromolecules.
The irreversible binding of chlorpromazine radical cation (CPZ+.) and photoactivated chlorpromazine (CPZ) to calf thymus DNA in vitro and bacterial macromolecules in intact bacterium cells was investigated. CPZ+. may be formed in vivo metabolically and photochemically. CPZ+. and photo-activated CPZ bind covalently to double- and single-strand DNA. The conformation of the DNA appeared to be important for the CPZ+. reactivity: though CPZ+. is less stabilized by complex formation with single-strand DNA, the reaction rate and the binding capacity of DNA-complexed CPZ+. with single-strand DNA is larger than with double-strand DNA. Photoactivated CPZ binds considerably to proteins, DNA and RNA in the intact bacterium cells. In spite of the relatively short lifetime of CPZ+. in the presence of the cells CPZ+. also binds irreversibly to bacterial DNA, RNA and proteins. The consequences of covalent binding for the cytotoxicity and genotoxicity of CPZ+. and photoactivated CPZ and the possible role for CPZ+. as an intermediate in the photobinding of CPZ is discussed.
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002250:Carbon Radioisotopes; D002414:Cations, Monovalent; D002417:Cattle; D002746:Chlorpromazine / Q000378:metabolism* / Q000528:radiation effects; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D006735:Horseradish Peroxidase; D007700:Kinetics; D009691:Nucleic Acid Denaturation; D010777:Photochemistry; D012329:RNA, Bacterial / Q000378:metabolism; D013950:Thymus Gland
D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D002414:Cations, Monovalent; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D004247:DNA; D006735:Horseradish Peroxidase; D002746:Chlorpromazine