title: Susceptibility factors and DNA adducts in peripheral blood mononuclear cells of aluminium smelter workers exposed to polycyclic aromatic hydrocarbons.
abstract: Formation of DNA adducts as a result of exposure to polycyclic aromatic hydrocarbons (PAH) was studied in 98 potroom workers from an aluminium smelting plant and in 55 blue-collar workers without occupational PAH exposure. DNA from peripheral blood mononuclear cells (PBMC) was used for quantitation of individual PAH-DNA adducts by 32P-postlabelling/high performance liquid chromatography (HPLC) analysis. Four individual DNA adducts (denoted A, B, C and D) were quantified in 141 of a total of 153 subjects. Genetic polymorphisms for cytochrome P-4501A1 ( CYP1A1), microsomal epoxide hydrolase, N-acetyltransferase 2, glutathione transferases M1, P1 and T1 ( GSTM1, GSTP1 and GSTT1, respectively) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were analysed. For 52 subjects, analysis of mRNA inducibility of CYP1A1 was performed. No statistically significant differences in the levels of total or individual DNA adducts A, C and D were found between potroom workers and control subjects. All potroom workers and the subgroup of potroom workers who reported to never/sometimes use personal respiratory protection ( n=72) were found to have a significantly higher likelihood of having high levels of adduct B than control subjects [odds ratio (OR) =3.4 with 95% confidence interval (CI) of 1.3-9.2, and OR=4.2 with 95% CI 1.6-11.5, respectively]. In the subgroup, levels of adducts A and B were found to be significantly higher among workers with employment time of less than 6 months ( n=5). Also, the levels of the individual DNA adducts were to some extent modified by genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and NQO1 and by CYP1A1 inducibility. In conclusion, levels of adduct B, identified by 32P-postlabelling/HPLC methodology as an indicator of PAH exposure in aluminium production, were modified by the use of respiratory protection, length of employment and genetic polymorphisms.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
authors.forename: Rainer
authors.initials: R
authors.lastname: Tuominen
authors.forename: Pawel
authors.initials: P
authors.lastname: Baranczewski
authors.forename: Margareta
authors.initials: M
authors.lastname: Warholm
authors.forename: Lars
authors.initials: L
authors.lastname: Hagmar
authors.forename: Lennart
authors.initials: L
authors.lastname: Möller
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
mesh_terms: D000535:Aluminum; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D018736:DNA Adducts / Q000097:blood*; D004798:Enzymes / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008669:Metallurgy; D009784:Occupational Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D016273:Occupational Exposure; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D018736:DNA Adducts; D004798:Enzymes; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D000535:Aluminum; D019363:Cytochrome P-450 CYP1A1