Role of Ring Oxidation in the Metabolic Activation of 1-Nitropyrene

Nitropyrenes are a class of chemicals found in diesel engine exhaust that can form DNA adducts and are suspected animal carcinogens. Dr. Beland at the University of Arkansas for Medical Sciences examined the relationship between DNA adducts and cancer in laboratory animals treated with 1-nitropyrene, the major nitropyrene present in diesel engine exhaust. The investigator used state-of-the-art techniques to study DNA adducts formed from 1-nitropyrene under different conditions of exposure, with an emphasis on identifying unique adducts that had not been recognized before. First, he synthesized metabolites (products of biotransformation) of 1-nitropyrene that might form naturally in living cells. He then characterized the kinds of adducts found when these metabolites were combined with DNA in a test tube or with animal cells in culture. He also studied the types of DNA adducts formed in rat and mouse organs in which tumors have been found after 1-nitropyrene dissolved in dimethylsulfoxide was administerd to the newborn pups.