MOLECULAR DOSIMETRY OF DNA-DAMAGE INDUCED BY POLYCYCLIC AROMATIC-HYDROCARBONS - RELEVANCE FOR EXPOSURE MONITORING AND RISK ASSESSMENT

Polycyclic aromatic hydrocarbons (PAH) form a large group of organic c hemicals that are widely distributed in our environment as pollutants of air, water and soil, Several PAH are carcinogenic in rodents, while exposure to these compounds has been associated with various types of human cancer. Upon entering the body, PAH may be converted into react ive electrophilic species, which can give rise to the formation of DNA adducts. DNA adduct formation is considered to be the initial event i n chemical carcinogenesis. In this paper, two methods are illustrated that are widely used to determine PAH-DNA adduct formation, namely P-3 2-postlabelling, and immunochemical analysis with specific antibodies. The applications of the P-32-postlabelling assay comprise the followi ng: A study of interspecies differences in PAH bioactivation in vitro, with microsomal preparations isolated from liver tissue of various ro dent species and of human origin: the results indicate that there are considerable qualitative differences between the adduct patterns obtai ned, which is relevant with respect to extrapolation from animal to ma n. The analysis of DNA adduct formation in fish retrieved from marine environments polluted to various extents with PAH; results of these st udies show a correlation between liver-DNA adduct levels in these fish and the degree of PAH contamination in the aquatic environment. Biomo nitoring of PAH exposure through analysis of adducts in blood cells ob tained from heavy and light smokers; the data show a fair correlation between PAH-DNA adduct levels in white blood cells and cotinine conten t in blood plasma, the latter being used as a marker for exposure to c igarette smoke, The activity of the detoxifying enzyme glutathione S-t ransferase M1 (GSTM1) was also determined in these individuals. Immuno chemical analysis with a benzo(a)pyrene(BP)DNA-specific antiserum was used to investigate BP-adduct induction in situ, in different epitheli al cell types-basal/non-basal cells-of hamster trachea exposed to BP i n vitro, Histochemical staining of cell-specific cytokeratins was comb ined with adduct-specific immunostaining, The latter was quantified by immunofluorescence microscopy. The results show that removal of DNA a dducts from the basal cells is more rapid during the first 24 h follow ing exposure than from the non-basal cells. The sensitive methods for molecular dosimetry of DNA damage, as illustrated in this paper, appea r suitable for determining exposure of animals and humans to PAH, Furt her animal experiments and in vitro model studies will provide useful additional information that will help evaluate the relevance of biomon itoring data with respect to the health risk that may be associated wi th the exposure.