Myers S R, Flesher J W
Department of Pharmacology, A.B. Chandler Medical Center, University of Kentucky, Lexington 40536.
Chem Biol Interact. 1991;77(2):203-21. doi: 10.1016/0009-2797(91)90074-h.
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.
多核芳香烃屈在体外、大鼠肝细胞溶胶制剂中以及体内、大鼠背部皮下组织中会发生生物烷基化取代反应，生成6-甲基屈作为代谢产物。此外，在这些组织中还发现5-甲基屈和6-甲基屈都会发生脱烷基化反应生成屈，以及发生生物氧化反应生成相应的羟烷基取代屈和生物烷基化反应生成二甲基取代屈。5-甲基屈在这些组织中酶促环化生成4,5-亚甲基屈衍生物，它是苯并[a]芘的类似物。5,6-二甲基屈代谢生成单甲基屈、屈以及羟烷基取代屈。结果表明，在最高生化反应活性中心进行甲基的化学或生化取代可能是这些化合物及其亚甲基桥连代谢产物代谢活化和致癌性的必要步骤。
