Identification of Mutagenic Metabolites of lndeno[1,2,3-cd]pyrene Formed in Vitro with Rat Liver Enzymes1

MATERIALS AND METHODS lndeno[1,2,3-cd]pyrene (IP) is a major environmental pollutant which is carcinogenic on mouse skin and in rat lung. Unlike benzo(a)pyrene, IP is a nonaltemant polycyclic aromatic hydro carbon which is devoid of a bay region. IP was mutagenic in Salmonella typhimurium TA100 in the presence of a 9000 x g supernatant from the livers of Aroclor-pretreated rats. Using a similar activation system, the major metabolites of IP were isolated and identified by comparison with synthetic reference standards, frans-1,2-Dihydro-1,2-dihydroxy-IP, 8-, 9-, and 10hydroxy-IP, 8and 9-hydroxy-frans-1,2-dihydro-1,2-dihydroxyIP, and IP-1,2-quinone are among the metabolites formed in vitro. The 1,2-epoxide of indeno[1,2,3-cd]pyrene is a potent direct-acting mutagen. 8and 9-hydroxy-IP were mutagenic with metabolic activation. 1-, 2-, and 6-hydroxy-IP and the frans-1,2dihydrodiol had no significant mutagenic activity in S. typhimu rium TA100 with metabolic activation. These data suggest that the K-region oxides of IP and of 8and 9-hydroxy-IP are ulti mately responsible for its mutagenic activity.