Prostaglandin H synthase (PGH) is an oxidative microsomal enzyme system separate from the cytochrome P450 system most often used for oxidative metabolism of xenobiotics. PGH derived from ram seminal vesicles has been used in the past to metabolize a number of polycyclic aromatic hydrocarbon bay-region epoxides and aromatic amines to mutagens for Salmonella typhimurium. It was recently shown that PGH can metabolize a number of aromatic amines of the carboline and azaimidaozoarene classes that are formed during the cooking of beef to DNA-binding intermediates. Four of these chemicals, Trp-P-1, Trp-P-2, IQ, and MeIQ, which are potent mutagens in the presence of rat liver S-9, were tested with PGH. Mutagenicity was not obtained at doses comparable to those used with S-9. All four chemicals were direct-acting mutagens at doses 1000x those used with S-9. At these higher doses, PGH slightly enhanced the direct mutagenicity of Trp-P-2, had no effect on Trp-P-1, and decreased the mutagenicities of IQ and MeIQ. The direct-acting and PGH- mediated mutagenicity were highly dependent on pH and buffer composition.
