Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers

Abstract

This study investigated nucleic acid oxidation associated with styrene exposure, mRNA expression levels of hOGG1 gene and the role of the genetic polymorphism Ser326Cys of human 8-oxoguanine DNA N-glycosylase 1 ( hOGG1) in 60 styrene-exposed workers and 50 unexposed clerks. Biomarkers of exposure (styrene in blood, mandelic and phenylglyoxylic acids and 4-vinylphenol in urine) and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2′-deoxyguanosine (U-8-oxodGuo), 8-oxo-7,8-dihydroguanosine (U-8-oxoGuo) and 8-oxo-7,8-dihydroguanine (U-8-oxoGua) were determined by liquid chromatography–tandem mass spectrometry. The levels of 8-oxodGuo adduct and 2′-deoxyguanosine (dGuo) were measured by HPLC in DNA from white blood cells (WBC). Genomic DNA and RNA from blood samples were used to characterize the Ser326Cys polymorphism and the mRNA expression levels of the hOGG1 gene, respectively, by PCR-based methods. Exposed workers showed lower values of 8-oxodGuo/10 5 dGuo ratio in WBC-DNA but higher concentrations of U-8-oxoGuo compared to controls ( p = 0.002 and p = 0.008, respectively, t-test for independent samples). In the whole group, all urinary biomarkers of nucleic acid oxidation correlated with both the sum of mandelic and phenylglyoxylic acids ( rho > 0.33, p < 0.0001) and 4-vinylphenol ( rho > 0.29, p < 0.001), whereas 8-oxodGuo/10 5 dGuo in WBC showed a negative correlation with exposure parameters ( rho < −0.24, p < 0.02). Subjects bearing the hOGG1 Ser/Ser genotype showed lower values of 8-oxodGuo/10 5 dGuo in WBC than those with at least one variant Cys allele (0.34 ± 0.16 vs 0.45 ± 0.21, p = 0.008). In the subgroup of hOGG1 Ser/Ser subjects, laminators showed lower levels of WBC 8-oxodGuo/10 5 dGuo ratio and significantly higher concentrations of U-8-oxoGua than controls ( p = 0.07 and p = 0.01, respectively, t-test for independent samples). Interestingly, workers showed higher levels of hOGG1 expression compared to controls ( p < 0.0005). Styrene exposure seems to be associated with oxidation damage to nucleic acids, particularly to RNA and with an induction of the BER system.