title: Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers.
abstract: Waste incinerating workers are exposed to various pyrolysis products including polycyclic aromatic hydrocarbons (PAHs). We examined their PAH exposure by assessing urinary 1-hydroxypyrene glucuronide (1-OHPG), as a measure of internal dose, and aromatic DNA adducts in peripheral white blood cells (WBCs), as a measure of biological effect dose. The potential effect of genetic polymorphisms of three enzymes involved in PAH metabolisms (i.e., CYP1A1, GSTM1, and GSTT1) on these exposure markers was also investigated.Twenty-nine employees including workers incinerating industrial wastes and 21 non-exposed on-site controls were recruited from a company handling industrial wastes in South Korea. Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects working near incinerators. Urinary 1-OHPG was assayed by synchronous fluorescence spectroscopy (SFS) after immunoaffinity purification using monoclonal antibody 8E11. Aromatic DNA adducts in peripheral WBC were measured by the nuclease P1-enhanced post-labelling assay. Genotypes were assessed by PCR-based methods. Information on smoking habits and use of personal protective equipment were collected by self-administered questionnaire. Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (P=0.006, by Kruskal-Wallis test). A statistically significant dose-response increase in 1-OHPG levels was seen with the number of cigarettes consumed per day (r=0.686, P<0.001). Smoking and GSTM1 genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R(2)=0.565, P<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R(2)=0.249, P=0.201). Aromatic DNA adducts were significantly correlated with log-transformed urinary 1-OHPG level (r=0.31, P=0.04). However, the partial correlation coefficient adjusting for age, sex, and cigarette consumption was not significant (r=0.15, P=0.17). The significant association exists only in individuals with the GSTM1 null genotype (Pearson's correlation coefficient, r=0.52, P=0.01; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.36, P=0.04). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTM1 genotype. These results remain to be confirmed in future larger studies.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, 110-799, Seoul, South Korea.
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Lee
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ichiba
authors.forename: Jiusong
authors.initials: J
authors.lastname: Zhang
authors.forename: Katsumaro
authors.initials: K
authors.lastname: Tomokuni
authors.forename: Eung Soo
authors.initials: ES
authors.lastname: Hwang
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Mina
authors.initials: M
authors.lastname: Ha
authors.forename: SungGyun
authors.initials: S
authors.lastname: Kim
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Han
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Choi
authors.forename: Eunil
authors.initials: E
authors.lastname: Lee
authors.forename: Jae-yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Paul T
authors.initials: PT
authors.lastname: Strickland
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Soo-Hun
authors.initials: SH
authors.lastname: Cho
mesh_terms: D018736:DNA Adducts / Q000032:analysis; D005838:Genotype; D005965:Glucuronates / Q000652:urine*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D017745:Incineration; D019570:Inhalation Exposure; D007723:Korea; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism; D009153:Mutagens / Q000032:analysis; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000737:chemistry; D011110:Polymorphism, Genetic; D011721:Pyrenes; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects; D013223:Statistics as Topic
chemical_list: D018736:DNA Adducts; D005965:Glucuronates; D005982:Glutathione Transferase; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C093851:1-hydroxypyrene-glucuronide