DEVELOPMENT AND APPLICATION OF NONINVASIVE BIOMARKERS FOR CARCINOGEN-DNA ADDUCT ANALYSIS IN OCCUPATIONALLY EXPOSED POPULATIONS

Biological monitoring of exposures to carcinogenic compounds in the wo rkplace can be a valuable adjunct to environmental sampling and occupa tional medicine. Carcinogen-DNA adduct analysis has promise as a bioma rker of effective dose if target organ samples can be obtained non-inv asively. We have developed non-invasive techniques using exfoliated ur othelial and bronchial cells collected in urine and sputum, respective ly. First morning urine samples were collected from 33 workers exposed to benzidine or benzidine-based dyes and controls matched for age, ed ucation, and smoking status. Sufficient DNA for P-32-postlabelling ana lysis was obtained from every sample. Mean levels of a specific DNA ad duct (which co-chromatographed with standard characterized by MS) were elevated significantly in the benzidine-exposed workers relative to c ontrols, In addition, workers exposed to benzidine had higher adduct l evels than those exposed to benzidine-based dyes. This study demonstra tes the usefulness of these non-invasive techniques for exposure/effec t assessment. To be useful in occupational studies, biomarkers must al so be sensitive to exposure interventions. We have conducted topical a pplication studies of used gasoline engine oils in mice and found that the levels of carcinogen-DNA adducts in skin and lung can be signific antly lowered if skin cleaning is conducted in a timely manner. The co mbination of useful, non-invasive techniques to monitor exposure and e ffect and industrial hygiene interventions can be used to detect and p revent exposures to a wide range of carcinogens including those found in used gasoline engine oils and jet exhausts.