title: Molecular dosimetry of DNA damage induced by polycyclic aromatic hydrocarbons; relevance for exposure monitoring and risk assessment.
abstract: Polycyclic aromatic hydrocarbons (PAH) form a large group of organic chemicals 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 reactive electrophilic species, which can give rise to the formation of DNA adducts. DNA adduct formation is considered to be the initial event in chemical carcinogenesis. In this paper, two methods are illustrated that are widely used to determine PAH-DNA adduct formation, namely 32P-postlabelling, and immunochemical analysis with specific antibodies. The applications of the 32P-postlabelling assay comprise the following: A study of interspecies differences in PAH bioactivation in vitro, with microsomal preparations isolated from liver tissue of various rodent species and of human origin; the results indicate that there are considerable qualitative differences between the adduct patterns obtained, which is relevant with respect to extrapolation from animal to man. The analysis of DNA adduct formation in fish retrieved from marine environments polluted to various extents with PAH; results of these studies show a correlation between liver-DNA adduct levels in these fish and the degree of PAH contamination in the aquatic environment. Biomonitoring of PAH exposure through analysis of adducts in blood cells obtained from heavy and light smokers; the data show a fair correlation between PAH-DNA adduct levels in white blood cells and cotinine content in blood plasma, the latter being used as a marker for exposure to cigarette smoke.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Genetic Toxicology, TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Baan
authors.forename: M J
authors.initials: MJ
authors.lastname: Steenwinkel
authors.forename: P T
authors.initials: PT
authors.lastname: van den Berg
authors.forename: R
authors.initials: R
authors.lastname: Roggeband
authors.forename: J H
authors.initials: JH
authors.lastname: van Delft
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003367:Cotinine / Q000097:blood; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism; D004249:DNA Damage; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000009:adverse effects; D005982:Glutathione Transferase / Q000097:blood; D006801:Humans; D011083:Polycyclic Compounds / Q000009:adverse effects* / Q000097:blood; D012907:Smoking / Q000009:adverse effects
chemical_list: D018736:DNA Adducts; D004785:Environmental Pollutants; D011083:Polycyclic Compounds; D005982:Glutathione Transferase; D003367:Cotinine