P-32 POSTLABELING OF AROMATIC DNA-ADDUCTS IN WHITE BLOOD-CELLS AND ALVEOLAR MACROPHAGES OF SMOKERS - SATURATION AT HIGH EXPOSURES

DNA adducts may serve as a molecular dosimeter of exposure to cigarett e smoke-associated carcinogens such as polycyclic aromatic hydrocarbon s (PAH). Target tissues for cigarette smoke-induced carcinogenesis are rarely accessible; therefore, peripheral blood cells or cells obtaine d by bronchoalveolar lavage (BAL) may be used as surrogate sources of exposed DNA. However, the relationship between cigarette smoke exposur e and aromatic-DNA adducts in white blood cells and BAL cells is still unclear. In this study, we examined DNA adduct formation in lymphocyt es and BAL cells in several populations of smoking individuals by mean s of P-32-postlabelling. Significant correlations between the amount o f cigarettes smoked per day and the level of aromatic-DNA adducts were found in lymphocytes. In BAL cells, DNA adduct levels were associated with age (p = 0.05) and gender (p = 0.10) after adjustment for smokin g behaviour. Adduct formation levelled off at higher exposure levels, suggesting less efficient adduct formation; decreases in the formation of adducts per unit of exposure were found in lymphocytes (r(s) = -0. 80, p < 0.001) and BAL cells (r(s) = -0.72, p < 0.001). To assess intr a-individual variation in adduct levels at constant smoking behaviour, sampling was repeated after a period of 2 and 6 months, In lymphocyte s, repeated measurements with an interval of 2 months were highly corr elated (r = 0.84, p = 0.009, n = 8), whereas repeated measurements wit h an interval of 6 months showed no correlation (r = 0.30, p = 0.27, n = 16). Repeated measurements in BAL cells showed a significant correl ation after 6 months (r = 0.68, p = 0.03, n = 10). Furthermore, in a g roup of occupationally exposed aluminium workers, adduct levels in tot al white blood cells were correlated with the average concentrations o f PAH in the ambient air of workers who smoked cigarettes, whereas in non-smokers, no such relationship was found. We conclude that cigarett e smoking may directly or indirectly influence DNA adduct levels and s aturation of DNA adduct formation may occur, leading to non-linear dos e-response relationships.