OXIDATION OF 9-ALKYLANTHRACENES BY P450 2B1, HORSERADISH-PEROXIDASE, AND IRON TETRAPHENYLPORPHINE IODOSYLBENZENE SYSTEMS - ANAEROBIC AND AEROBIC MECHANISMS

Variously substituted alkylanthracenes were studied as models for poly cyclic hydrocarbon oxidations; 9-Methylanthracene was oxidized to 9-(h ydroxymethyl)anthracene, 10-methyl-10-hydroxy-9-anthrone, and anthraqu inone in several systems, including (i) NADPH- and O-2-fortified rat l iver microsomes, (ii) cytochrome P450 (P450) 2B1 supported by either i odosylbenzene (PhIO) or a mixture of NADPH-P450 reductase, NADPH, and O-2, (iii) horseradish peroxidase and either H2O2 or ethyl hydroperoxi de, and (iv) a mixture of iron tetraphenylporphine (FeTPP) and PhIO (i n anhydrous CH2Cl2/MeOH). The microsomal system also formed dihydrodio ls from 9-methyl- and 9-ethylanthracenes. The formation of the three o xidized products by the P450/NADPH/O-2 system was dependent upon O-2, label from O-18(2) was incorporated into the products, and no label fr om (H2O)-O-18 was incorporated. No label from O-18(2) was incorporated into the three products in the FeTPP/PhIO system. In the horseradish peroxidase/H2O2 system, the formation of the three products was decrea sed when O-2 was omitted, and label from both (H2O)-O-18 and O-18(2) w as incorporated into all three products. The results are interpreted i n terms of three mechanisms. One is used by the FeTPP and P450 systems , with all oxygen transfers coming from an FeO entity. The other two p athways are utilized by horseradish peroxidase and begin with formatio n of a radical cation, which can undergo reactions either with H2O or with O-2 to form the products detected here. The involvement of a 9-me thylanthracene radical cation in the P450 and FeTPP pathways is a poss ibility, but rapid rearrangement and oxygen rebound must be invoked. C omparisons of products from various 9-alkylanthracenes do not provide evidence that one-electron oxidation is an integral part of the epoxid ation process with these compounds. The significance of the lack of tr apping of' radical (by (H2O)-O-18) in the P450 reactions to DNA adduct formation is considered.