CYTOCHROME P450-MEDIATED ACTIVATION OF PHENANTHRENE IN GENETICALLY-ENGINEERED V79 CHINESE-HAMSTER CELLS

V79 Chinese hamster cells genetically engineered for rat cytochromes P 450 1A1, 1A2, 2B1 and human cytochromes P450 1A1, 1A2, 2A6, 2E1, and 3 A4 are being applied in metabolism studies on polycyclic aromatic hydr ocarbons. This study presents the results on phenanthrene as the proto typic polycyclic aromatic hydrocarbon possessing a bay region. Phenant hrene is of less importance regarding cytotoxicity and carcinogenicity as compared to e.g. benzo[a]pyrene or 7,12-dimethylbenz[a]anthracene. However, phenanthrene is more readily converted to metabolites which are excreted in higher amounts than those from any other polycyclic ar omatic hydrocarbon. Therefore, its metabolites are of diagnostic value in epidemiological and occupational exposure studies. For this reason , it is worthwhile to understand the metabolism of phenanthrene in det ail, e.g. allocating metabolites and cytochromes P450s. In accordance to previous observations cytochromes P450 1A1 and 1A2 were the most ac tive forms towards phenanthrene. However, metabolite profiles differed between rat and human homologues of cytochromes P450, in particular f or cytochrome P450 1A2. The predominant metabolite formed by rat cytoc hrome P450 1A2 was the K region trans-9,10-dihydrodiol, whereas human cytochrome P450 1A2 produced similar amounts of the trans-1,2-, trans- 3,4- and trans-9,10-dihydrodiol. High amounts of trans-1,2-dihydrodiol , the metabolic precursor of the bay-region dihydrodiol epoxide, were also formed by human cytochrome P450 1A1 compared to its rat homologue . Unexpectedly, human cytochrome P450 2E1 showed a remarkable catalyti c activity to metabolize phenanthrene to its trans-9,10-dihydrodiol. U tilizing recombinant CYPs in live V79 cells appears to be a valuable t ool yielding results important for the evaluation of exposure data and risk assessment for humans.