POLYCYCLIC AROMATIC-HYDROCARBONS (PAHS), NITRO-PAHS AND RELATED ENVIRONMENTAL COMPOUNDS - BIOLOGICAL MARKERS OF EXPOSURE AND EFFECTS

Lung cancer caused by polycyclic aromatic hydrocarbons (PAHs), nitro-P AHs and related environmental agents is a major problem in industriali zed nations. The high case-fatality rate of the disease, even with the best supportive treatment, underscores the importance of primary lung cancer prevention. Development of biomarkers of exposure and effects to PAHs and related compounds is now underway and includes measurement of urinary metabolites of specific PAHs as well as detection of prote in and DNA adducts as indicators of effective dose. Validation of thes e markers in terms of total environmental dose requires that concurren t measures of air levels and potential dermal exposure be made. In add ition, the interrelationships between PAH biomarkers must be determine d, particularly when levels of the marker in surrogate molecules (e.g. , protein) or markers from surrogate tissues (e.g., lymphocyte DNA) ar e used to assess the risk to the target organ, the lung. Two approache s to biomarker studies will be reviewed in this article: the progress made using blood lymphocytes as surrogates for lung tissues and the pr ogress made developing noninvasive markers of carcinogen-DNA adduct le vels in lung-derived cells available in bronchial-alveolar lavage and in sputum. Data are presented from studies in which exfoliated urothel ial cells were used as a surrogate tissue to assess exposure to human urinary bladder carcinogens in occupational groups.