Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

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• 作者：Fabrizio Palumbo^a ; Guillermo Garcia-Lainez^b ; Daniel Limones-Herrero^a ; M. Dolores Coloma^b ; Javier Escobar^b ; M. Consuelo Jimé ; nez^a ; Miguel A. Miranda^a ; ^{mmiranda@qim.upv.es} ; Inmaculada Andreu^a ; ^b ; ^{iandreur@qim.upv.es}
• 关键词：CPZ ; chlorpromazine ; PMZ ; promazine ; DMCPZ ; demethylchlorpromazine ; DDMCPZ ; didemethylchlorpromazine ; CPZSO ; chlorpromazine sulfoxide ; EPR ; electron paramagnetic resonance ; Fpg ; E. coli formamidopyrimidine DNA glycosylase ; Endo III ; E. coli endonuclease III ; Endo V ; T4 endonuclease V ; FSK ; fibroblasts ; DMEM ; Dulbecco's modified eagle medium ; FBS ; fetal bovine serum ; TAE ; tris-acetate-EDTA ; MNP ; 2-methyl-2-nitrosopropane ; NRU ; neutral red uptake ; PIF ; photo-irritation-factor
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2016
• 出版时间：15 December 2016
• 年：2016
• 卷：313
• 期：Complete
• 页码：131-137
• 全文大小：945 K
• 卷排序：313

文摘

Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. DNA single strand breaks formation is observed on agarose gel electrophoresis. Photochemical and EPR studies support generation of aryl radicals by C-Cl cleavage. The aminoalkyl side chain of metabolites modulates the photo(geno)toxic potential.