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Influence of genetic polymorphisms of biotransformation enzymes on gene mutations, strand breaks of deoxyribonucleic acid, and micronuclei in mononuclear blood cells and urinary 8-hydroxydeoxyguanosine in potroom workers exposed to polyaromatic hydrocarbons

Carstensen, U; Hou, S M; Alexandrie, A K; Hogstedt, B; Tagesson, C; Warholm, M; Rannug, A; Lambert, B; Axmon, Anna LU and Hagmar, L (1999) In Scandinavian Journal of Work, Environment and Health 25(4). p.351-360
Abstract
OBJECTIVES: Airborne exposure to polycyclic aromatic hydrocarbons (PAH) in the potroom of an aluminum reduction plant was studied in relation to genotoxic or mutagenic effects, and the possibility of host genotypes of different metabolizing enzymes modifying associations between PAH exposure and genotoxic or mutagenic response was assessed. SUBJECTS AND METHODS: Ninety-eight male potroom workers and 55 male unexposed blue-collar workers constituted the study population. Micronuclei in CD4+ and CD8+ lymphocytes, DNA (deoxyribonucleic acid) single-strand breaks, hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation frequency, and genotype for cytochrome P-4501A1, glutathione transferases M1, T1 and P1, and microsomal epoxide... (More)
OBJECTIVES: Airborne exposure to polycyclic aromatic hydrocarbons (PAH) in the potroom of an aluminum reduction plant was studied in relation to genotoxic or mutagenic effects, and the possibility of host genotypes of different metabolizing enzymes modifying associations between PAH exposure and genotoxic or mutagenic response was assessed. SUBJECTS AND METHODS: Ninety-eight male potroom workers and 55 male unexposed blue-collar workers constituted the study population. Micronuclei in CD4+ and CD8+ lymphocytes, DNA (deoxyribonucleic acid) single-strand breaks, hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation frequency, and genotype for cytochrome P-4501A1, glutathione transferases M1, T1 and P1, and microsomal epoxide hydrolase were analyzed using peripheral mononuclear cells. Urine samples were collected for the analysis of 8-hydroxydeoxyguanosine. RESULTS: Micronuclei in peripheral CD4+ and CD8+ lymphocytes, DNA single-strand breaks, HPRT mutation frequency, and 8-hydroxydeoxyguanosine in urine did not differ between the potroom workers and the unexposed referents. With the exception of an observed exposure-response relationship for potroom workers with Tyr/Tyr genotype for microsomal epoxide hydrolase, between airborne PAH and CD8+ micronuclei, no correlations were found between any of the genotoxicity biomarkers and any of the exposure measures (airborne particulate PAH, airborne gas phase PAH, length of employment in the potroom, 1-hydroxypyrene in urine, or PAH-DNA adducts in peripheral lymphocytes), also when genotypes for biotransforamtion enzymes were considered. CONCLUSIONS: The results indicate that the employed biomarkers of mutagenic or genotoxic effects are not appropriate for surveillance studies of potroom workers exposed to current airborne levels of PAH. The significance of the correlation between airborne PAH and CD8+ micronuclei in Tyr/Tyr genotype subjects should be evaluated. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
glutathione transferases, cytochrome P-4501A1, biomarkers of genotoxic effect, aluminum reduction plant, microsomal epoxide hydrolase, peripheral lymphocyte
in
Scandinavian Journal of Work, Environment and Health
volume
25
issue
4
pages
351 - 360
publisher
Finnish Institute of Occupational Health
external identifiers
  • pmid:10505661
  • scopus:0032830142
ISSN
0355-3140
language
English
LU publication?
yes
id
67613416-01a3-4f6d-abf2-8ac2377240e7 (old id 1115689)
date added to LUP
2008-07-08 11:43:31
date last changed
2017-02-12 03:32:56
@article{67613416-01a3-4f6d-abf2-8ac2377240e7,
  abstract     = {OBJECTIVES: Airborne exposure to polycyclic aromatic hydrocarbons (PAH) in the potroom of an aluminum reduction plant was studied in relation to genotoxic or mutagenic effects, and the possibility of host genotypes of different metabolizing enzymes modifying associations between PAH exposure and genotoxic or mutagenic response was assessed. SUBJECTS AND METHODS: Ninety-eight male potroom workers and 55 male unexposed blue-collar workers constituted the study population. Micronuclei in CD4+ and CD8+ lymphocytes, DNA (deoxyribonucleic acid) single-strand breaks, hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation frequency, and genotype for cytochrome P-4501A1, glutathione transferases M1, T1 and P1, and microsomal epoxide hydrolase were analyzed using peripheral mononuclear cells. Urine samples were collected for the analysis of 8-hydroxydeoxyguanosine. RESULTS: Micronuclei in peripheral CD4+ and CD8+ lymphocytes, DNA single-strand breaks, HPRT mutation frequency, and 8-hydroxydeoxyguanosine in urine did not differ between the potroom workers and the unexposed referents. With the exception of an observed exposure-response relationship for potroom workers with Tyr/Tyr genotype for microsomal epoxide hydrolase, between airborne PAH and CD8+ micronuclei, no correlations were found between any of the genotoxicity biomarkers and any of the exposure measures (airborne particulate PAH, airborne gas phase PAH, length of employment in the potroom, 1-hydroxypyrene in urine, or PAH-DNA adducts in peripheral lymphocytes), also when genotypes for biotransforamtion enzymes were considered. CONCLUSIONS: The results indicate that the employed biomarkers of mutagenic or genotoxic effects are not appropriate for surveillance studies of potroom workers exposed to current airborne levels of PAH. The significance of the correlation between airborne PAH and CD8+ micronuclei in Tyr/Tyr genotype subjects should be evaluated.},
  author       = {Carstensen, U and Hou, S M and Alexandrie, A K and Hogstedt, B and Tagesson, C and Warholm, M and Rannug, A and Lambert, B and Axmon, Anna and Hagmar, L},
  issn         = {0355-3140},
  keyword      = {glutathione transferases,cytochrome P-4501A1,biomarkers of genotoxic effect,aluminum reduction plant,microsomal epoxide hydrolase,peripheral lymphocyte},
  language     = {eng},
  number       = {4},
  pages        = {351--360},
  publisher    = {Finnish Institute of Occupational Health},
  series       = {Scandinavian Journal of Work, Environment and Health},
  title        = {Influence of genetic polymorphisms of biotransformation enzymes on gene mutations, strand breaks of deoxyribonucleic acid, and micronuclei in mononuclear blood cells and urinary 8-hydroxydeoxyguanosine in potroom workers exposed to polyaromatic hydrocarbons},
  volume       = {25},
  year         = {1999},
}