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

Objectives Airborne exposure to polycyclic aromatic hydrocarbons (PAH) in t he potroom of an aluminum reduction plant was studied in relation to genoto xic or mutagenic effects, and the possibility of host genotypes of differen t metabolizing enzymes modifying associations between PAH exposure and geno toxic or mutagenic response was assessed. Subjects and methods Ninety-eight male potroom workers and 55 male unexpose d 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 mononu clear cells. Urine samples were collected for the analysis of 8-hydroxydeox yguanosine. Results Micronuclei in peripheral CD4(+) and CD8(+) lymphocytes, DNA single -strand breaks, HPRT mutation frequency, and 8-hydroxydeoxyguanosine in uri ne did not differ between the potroom workers and the unexposed referents. With the exception of an observed exposure-response relationship for potroo m workers with Tyr/Tyr genotype for microsomal epoxide hydrolase, between a irborne PAH and CD8(+) micronuclei, no correlations were found between any of the,genotoxicity biomarkers and any of the exposure measures (airborne p articulate 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 potroo m workers exposed to current airborne levels of PAH. The significance of th e correlation between airborne PAH and CD8(+) micronuclei in Tyr/Tyr genoty pe subjects should be evaluated.