Conversion of 1-naphthol to naphthoquinone metabolites by rat liver microsomes: demonstration by high-performance liquid chromatography with reductive electrochemical detection.
1-Naphthol has recently been shown to be selectively toxic to short-term organ cultures of human colorectal tumor tissue. The mechanism underlying 1-naphthol's selective toxicity is as yet unknown, but may be due to the formation of naphthoquinone metabolites, which are known to be highly toxic to tumor cells. By using high-performance liquid chromatography with reductive electrochemical detection, it has been possible to show that 1-naphthol is converted to naphthoquinone metabolites by rat liver microsomes. At least two metabolic pathways, independent of cytochrome P-450, appear to be involved. Iron-dependent lipid peroxidation appears to be responsible for at least part of the conversion of 1-naphthol to predominantly 1,4-naphthoquinone, and it seems likely that superoxide anion radical generation by NADPH-cytochrome P-450 reductase could also catalyze this conversion. 1-Naphthol therefore seems to be converted to cytotoxic naphthoquinone metabolites by mechanism(s) dependent upon the generation of free radicals in rat liver microsomes. The results also demonstrate the utility of HPLC with reductive electrochemical detection for investigations of quinone metabolite formation and the measurement of quinones of both physiological and environmental interest.
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004563:Electrochemistry; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism* / Q000633:toxicity; D009285:Naphthoquinones / Q000096:biosynthesis* / Q000302:isolation & purification; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D009284:Naphthols; D009285:Naphthoquinones; C029350:1-naphthol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D007501:Iron