COMPARATIVE METABOLISM OF PHENANTHRO[3,4-B]THIOPHENE, PHENANTHRO[4,3-B]THIOPHENE AND THEIR CARBON ANALOG BENZO[C]PHENANTHRENE BY RAT LIVER MICROSOMES

Phenanthro[3,4-b]thiophene (P[3,4-b]T) and phenanthro[4,3-b]thiophene (P[4,3-b]T) are thiasters of weakly mutagenic benzo[c]phenanthrene (B[c]P). These polycyclic sulfur heterocycles (thia-PAHs) represent a group of chemicals which have been identified in cigarette smoke. P[3,4-b]T is a potent mutagen in Salmonella typhimurium strain TA100 in the presence of rat liver S9, whereas its isosteric isomer P[4,3-b]T is a nonmutagenic compound. In order to understand the mechanism underlying the differences in the mutagenic activity of P[3,4-b]T and P[4,3-b]T, we have investigated the metabolism of P[3,4-b]T, P[4,3-b]T, and their carbon analogue B[c]P by rat liver microsomes. The liver microsomes from rats treated with Aroclor 1254 metabolized P[3,4-b]T, P[3,4-b]T, and B[c]P at a rate nearly 7- to 9-fold greater than of the control liver microsomes. High-performance liquid chromatography (HPLC) analysis of the metabolites formed showed that B[c]P was metabolized almost exclusively to its dihydrodiols which compr...