Metabolism of chrysene, 5-methylchrysene, 6-methylchrysene and 5,6-dimethylchrysene in rat liver cytosol, in vitro, and in rat subcutaneous tissue, in vivo.
The polynuclear aromatic hydrocarbon chrysene undergoes a bioalkylation substitution reaction in vitro, in rat liver cytosol preparations, and in vivo, in rat dorsal subcutaneous tissue to yield 6-methylchrysene as a metabolite. In addition, both 5-methyl- and 6-methylchrysene were found to undergo a dealkylation reaction in these tissues to yield chrysene as well as both a biooxidation reaction to yield the corresponding hydroxyalkyl substituted chrysene and a bioalkylation reaction to give a dimethyl substituted chrysene. 5-Methylchrysene enzymatically cyclized to the 4,5-methylenechrysene derivative, an analog of benzo[a]pyrene in these tissues. 5,6-Dimethylchrysene was metabolized to monomethyl chrysenes, chrysene, and the hydroxyalkyl substituted chrysenes. The results suggest that chemical or biochemical substitution of a methyl group at the center of highest biochemical reactivity may be a necessary step in the metabolic activation and carcinogenicity of these compounds and their methylene bridged metabolites.
Myers
S R
SR
Department of Pharmacology, A.B. Chandler Medical Center, University of Kentucky, Lexington 40536.
Flesher
J W
JW
D000478:Alkylation; D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D002911:Chrysenes / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains
D002911:Chrysenes; C031180:chrysene; C043380:5,6-dimethylchrysene; C047249:6-methylchrysene; C008422:5-methylchrysene