Metabolism and Biological Effects of Nitropyrene and Related Compounds

This report describes a study by Dr. King to investigate in rats the carcinogenic properties of nitropyrene and related compounds and how these compounds are metabolically activated in target tissues. Nitropyrenes and related nitroaromatics are of interest because of their ubiquity in diesel emissions and reported carcinogenicity. In a series of experiments, 1,3-, 1,6-, and 1,8-dinitropyrene, 1-nitropyrene, and phenolic metabolites of 1-nitropyrene were administered to weanling and newborn rats separately and in mixtures by intraperitoneal injection, intragastric or oral intubation, or subcutaneous injection. Carcinogenicity was determined by the formation of tumors including malignant fibrous histiocytomas, mammary gland tumors, and leukemias. The relative carcinogenicities of the different compounds and the effect modification of the mode of administration and the age of the rats were compared. In order to measure how nitropyrenes may be metabolically activated in target tissue, a second set of biochemical experiments examined the capacity of cytosols and intact cell preparations of rat mammary glands to metabolize 1,3-, 1,6-, and 1,8-dinitropyrene, and 1-nitropyrene.