Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers

Jeongmi Lee, Daehee Kang, Kyoung Ho Lee, Masayoshi Ichiba, Jiusong Zhang, Katsumaro Tomokuni, Eung Soo Hwang, Chung Gyu Park, Mina Ha, SungGyun Kim, Sang Beom Han, Jae Wook Choi, Eun Il Lee, Jae Yeon Jang, Paul T. Strickland, Ari Hirvonen, Soo Hun Cho

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 R2 = 0.565, P < 0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R2 = 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.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume514
Issue number1-2
DOIs
Publication statusPublished - 2002 Feb 15

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Incineration
Polycyclic Aromatic Hydrocarbons
DNA Adducts
Industrial Waste
Genotype
Tobacco Products
Smoking
Leukocytes
National Institute for Occupational Safety and Health (U.S.)
Republic of Korea
Cytochrome P-450 CYP1A1
Fluorescence Spectrometry
Genetic Polymorphisms
Habits
polycyclic aromatic hydrocarbons-DNA adduct
Respiration
Monoclonal Antibodies
Regression Analysis
Polymerase Chain Reaction
Enzymes

Keywords

  • 1-Hydroxypyrene glucuronide
  • Aromatic DNA adducts
  • Genetic polymorphism
  • Incinerator
  • Polycyclic aromatic hydrocarbon

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers. / Lee, Jeongmi; Kang, Daehee; Lee, Kyoung Ho; Ichiba, Masayoshi; Zhang, Jiusong; Tomokuni, Katsumaro; Hwang, Eung Soo; Park, Chung Gyu; Ha, Mina; Kim, SungGyun; Han, Sang Beom; Choi, Jae Wook; Lee, Eun Il; Jang, Jae Yeon; Strickland, Paul T.; Hirvonen, Ari; Cho, Soo Hun.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 514, No. 1-2, 15.02.2002, p. 213-221.

Research output: Contribution to journalArticle

Lee, J, Kang, D, Lee, KH, Ichiba, M, Zhang, J, Tomokuni, K, Hwang, ES, Park, CG, Ha, M, Kim, S, Han, SB, Choi, JW, Lee, EI, Jang, JY, Strickland, PT, Hirvonen, A & Cho, SH 2002, 'Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 514, no. 1-2, pp. 213-221. https://doi.org/10.1016/S1383-5718(01)00340-0
Lee, Jeongmi ; Kang, Daehee ; Lee, Kyoung Ho ; Ichiba, Masayoshi ; Zhang, Jiusong ; Tomokuni, Katsumaro ; Hwang, Eung Soo ; Park, Chung Gyu ; Ha, Mina ; Kim, SungGyun ; Han, Sang Beom ; Choi, Jae Wook ; Lee, Eun Il ; Jang, Jae Yeon ; Strickland, Paul T. ; Hirvonen, Ari ; Cho, Soo Hun. / Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2002 ; Vol. 514, No. 1-2. pp. 213-221.
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T1 - Influence of GSTM1 genotype on association between aromatic DNA adducts and urinary PAH metabolites in incineration workers

AU - Lee, Jeongmi

AU - Kang, Daehee

AU - Lee, Kyoung Ho

AU - Ichiba, Masayoshi

AU - Zhang, Jiusong

AU - Tomokuni, Katsumaro

AU - Hwang, Eung Soo

AU - Park, Chung Gyu

AU - Ha, Mina

AU - Kim, SungGyun

AU - Han, Sang Beom

AU - Choi, Jae Wook

AU - Lee, Eun Il

AU - Jang, Jae Yeon

AU - Strickland, Paul T.

AU - Hirvonen, Ari

AU - Cho, Soo Hun

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N2 - 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 R2 = 0.565, P < 0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R2 = 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.

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KW - 1-Hydroxypyrene glucuronide

KW - Aromatic DNA adducts

KW - Genetic polymorphism

KW - Incinerator

KW - Polycyclic aromatic hydrocarbon

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