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- Carstensen, U, et al.
(författare)
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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
- 1999
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 25:4, s. 351-360
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Tidskriftsartikel (refereegranskat)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.
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- Erlinge, David, et al.
(författare)
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Phenotype changes of the vascular smooth muscle cell regulate P2 receptor expression as measured by quantitative RT-PCR
- 1998
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 248:3, s. 864-870
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Tidskriftsartikel (refereegranskat)abstract
- Studies using selective agonists have suggested that the contractile effect of extracellular nucleotides, such as ATP and UTP, in blood vessels is mediated mainly by P2X1 receptors with a smaller contribution of P2Y receptors while the mitogenic effect is mediated by P2Y (P2Y1, P2Y2, P2Y4, and P2Y6) receptors with no effect of P2X1 receptors. This indicates a difference in P2 receptor expression between the contractile and the synthetic phenotype of the SMC. To measure the expression of mRNA for these receptors a competitive RT-PCR assay was developed that utilised synthetic RNA-competitors allowing determination of the number of mRNA copies for each receptor in the samples. In the synthetic phenotype the mitogenic P2Y1 and P2Y2 receptor transcripts were upregulated by 342- and 8-fold, respectively, while the contractile P2X1 receptor is totally downregulated and the P2Y4 and P2Y6 receptors were unchanged. This plasticity of the receptor expression may be important in the transition from the contractile to the synthetic SMC phenotype.
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