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.
OBJECTIVE
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.


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.
Carstensen
U
U
Department of Occupational and Environmental Medicine, University Hospital, Umeå, Sweden.
Hou
S M
SM
Alexandrie
A K
AK
Högstedt
B
B
Tagesson
C
C
Warholm
M
M
Rannug
A
A
Lambert
B
B
Axmon
A
A
Hagmar
L
L
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D001711:Biotransformation; D002617:Chemical Industry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004587:Electrophoresis, Agar Gel; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006841:Hydrocarbons, Aromatic; D007963:Leukocytes, Mononuclear; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D009154:Mutation; D016273:Occupational Exposure; D011110:Polymorphism, Genetic
D015415:Biomarkers; D006841:Hydrocarbons, Aromatic; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D003849:Deoxyguanosine