Comparative studies of the metabolic activation of chrysene in rodent and human skin.
Metabolism and activation of chrysene was examined in mouse, rat and human skin using a short-term organ culture technique. Mouse skin released larger quantities of free dihydrodiols into the culture medium than either rat or human skin and greater quantities of chrysene metabolites became covalently bound to the DNA of mouse skin. The stereochemistry of the chrysene-1,2-diol that was formed by each skin type was examined using high-performance liquid chromatography (HPLC) with a chiral stationary phase to resolve the enantiomers. It was found that in each case the (-)-enantiomer predominated. When hydrolysates of DNA extracted from rodent or human skin that had been treated with 3H-labelled chrysene were chromatographed on Sephadex LH-20 columns, the elution profiles of the hydrocarbon-DNA adducts were found to vary between the species studied. Further examination using HPLC showed that some of the adducts formed in skin had the chromatographic characteristics of adducts formed when the anti-isomer of the 'bay-region' diol-epoxide of chrysene (r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene) reacted with DNA and that others had the characteristics of triol-epoxide adducts.
D000818:Animals; D001711:Biotransformation; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002911:Chrysenes / Q000378:metabolism*; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D010616:Phenanthrenes / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000378:metabolism*; D013237:Stereoisomerism
D002911:Chrysenes; D010616:Phenanthrenes; C031180:chrysene; D004247:DNA