Regio- and stereoselectivity of hepatic cytochrome P-450 toward polycyclic aromatic hydrocarbon substrates.

Abstract

Although the cytochrome P-450 system shows broad substrate specificity toward the PAH, it also has regio- and stereoselectivity. Of the PAH substrates yet studied, phenanthrene is metabolized most efficiently, whereas chrysene and DBA are much more slowly turned over. Interestingly, the cytochrome P-450 system and epoxide hydrolase favor the formation of dihydrodiols with R,R configuration. The predominant enantiomers of the dihydrodiols with the bay-region double bond, as well as bay-region diol epoxides derived from phenanthrene, chrysene, BA and B[a]P, are superimposable when their bay-regions are aligned (Fig. 3). These metabolically favored isomers of the dihydrodiols and bay-region diol epoxides are also the more carcinogenic isomers when derived from carcinogenic polycyclic hydrocarbons.