The Effects of Copollutants on the Metabolism and DNA Binding of Carcinogens

Research Report 66, May 1994

High doses of inhaled diesel engine exhaust produce lung tumors in laboratory animals and may cause cancer in humans. Nitropyrenes are products of diesel engine exhaust and can be activated by the body\'s metabolism to form highly reactive products that interact with DNA to form DNA adducts. The adducts can interfere with the normal processes of DNA replication and can lead to genetic mutations that may result in carcinogenesis. Dr. Howard and colleagues at Case Western Reserve University wanted to understand the way that metabolism and adduct formation of nitropyrenes may be affected by the presence of pyrene. The investigators conducted a pilot study using two approaches to examine the effects of pyrene on the metabolism of nitropyrene. First, they conducted in vitro studies to determine the extent to which 1-nitropyrene metabolism was inhibited by pyrene and other pollutants. In the second series of experiments, laboratory mice were exposed to 1-nitropyrene or 1,6-dinitropyrene alone or in the presence of possible copollutants such as pyrene or other nitropyrenes. The urine and feces of the mice were examined for metabolites of 1-nitropyrene or 1,6-dinitropyrene. In addition, mouse liver DNA was examined using two techniques for measuring the presence of DNA adducts.