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Susceptibility factors and DNA adducts in peripheral blood mononuclear cells of aluminium smelter workers exposed to polycyclic aromatic hydrocarbons

Tuominen, R; Baranczewski, P; Warholm, M; Hagmar, Lars LU ; Moller, L and Rannug, A (2002) In Archives of Toxicology 76(3). p.178-186
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 P-32-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 I (NQ01) were... (More)
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 P-32-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 I (NQ01) 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 P-32-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
polycyclic aromatic, lymphocytes, occupational health, DNA adducts, polymorphism, hydrocarbons
in
Archives of Toxicology
volume
76
issue
3
pages
178 - 186
publisher
Springer
external identifiers
  • pmid:11967624
  • wos:000175599500008
  • scopus:0036216412
ISSN
0340-5761
DOI
10.1007/s00204-002-0331-0
language
English
LU publication?
yes
id
b5b41d5a-5ea7-43b6-9236-f98dca2e91f9 (old id 337690)
date added to LUP
2007-11-09 14:31:15
date last changed
2017-02-12 04:15:49
@article{b5b41d5a-5ea7-43b6-9236-f98dca2e91f9,
  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 P-32-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 I (NQ01) 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 P-32-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.},
  author       = {Tuominen, R and Baranczewski, P and Warholm, M and Hagmar, Lars and Moller, L and Rannug, A},
  issn         = {0340-5761},
  keyword      = {polycyclic aromatic,lymphocytes,occupational health,DNA adducts,polymorphism,hydrocarbons},
  language     = {eng},
  number       = {3},
  pages        = {178--186},
  publisher    = {Springer},
  series       = {Archives of Toxicology},
  title        = {Susceptibility factors and DNA adducts in peripheral blood mononuclear cells of aluminium smelter workers exposed to polycyclic aromatic hydrocarbons},
  url          = {http://dx.doi.org/10.1007/s00204-002-0331-0},
  volume       = {76},
  year         = {2002},
}