Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene

Abstract

We evaluated glutathione transferase (GST) activities and the levels of glutathionylated hemoglobin in the RBC of 42 workers exposed to 1,3-butadiene in a petrochemical plant, using 43 workers not exposed to 1,3-butadiene and 82 foresters as internal and external controls, respectively. Median 1,3-butadiene exposure levels were 1.5, 0.4, and 0.1 Mg/m 3 in 1,3-butadieneexposed workers, in workers not directly exposed to 1,3-butadiene, and in foresters, respectively. In addition, we determined in the peripheral blood lymphocytes of the same individuals the presence of GST polymorphic genes GSTT1 and GSTM1 and the distribution of GSTP1 allelic variants. Comparing the mean values observed in petrochemical workers with those of control foresters, we found a marked decrease of GST enzymatic activity and a significant increase of glutathionylated hemoglobin in the petrochemical workers. A weak but significant negative correlation was found between levels of 1,3-butadiene exposure and GST activity, whereas a positive correlation was found between 1,3-butadiene exposure and glutathionylated hemoglobin. A negative correlation was also observed between GST activity and glutathionylated hemoglobin. No influence of confounders was observed. Using a multiple linear regression model, up to 50.6% and 41.9% of the variability observed in glutathionylated hemoglobin and GST activity, respectively, were explained by 1,3-butadiene exposure, working setting, and GSTT1 genotype. These results indicate that occupational exposure to 1,3-butadiene induces an oxidative stress that impairs the GST balance in RBC, and suggest that GST activity and glutathionylated hemoglobin could be recommended as promising biomarkers of effect in petrochemical workers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3004 -12)

Measurement of Glutathionylated Haemoglobin by MAL-DI-ToF Mass Spectrometry as a Biomarker of Oxidative Stress in Heavy Smokers and in Occupational Obese Subjects

“…The values measured are also lower than those measured in dialyzed (5% -20%; weighted mean 11.4%) [13,18] and diabetic (5% -11%; weighted mean 8.3%) [16,17,20] subjects and, for the group of smokers, approximately in the same range (7.2% ± 2.8%) of healthy subjects who are occupationally exposed to butadiene in chemical plants at airborne concentrations in the range 0.1 -200 μg/m 3 [19].…”

“…A total number of subjects approaching one thousand have been examined. The results of the studies published in the literature are collected in Table 1 (see references [12][13][14][15][16][17][18][19][20][21][22][23] therein).…”

Serum Cytokeratin 18 and Cytokine Elevations Suggest A High Prevalence of Occupational Liver Disease in Highly Exposed Elastomer/Polymer Workers

“…Specifically, genetic and nutritional susceptibility factors could be relevant for TASH just as they are in ASH and NASH (11, 19). Genetic polymorphisms in enzymes implicated in the metabolism of industrial chemicals (cytochrome P450 2E1, or Cyp2E1, and glutathione S-transferases, or GST) influenced chemical toxicity in previous studies (29, 30). Importantly, the 30% prevalence of suspected TASH in our study is similar to the previously reported prevalence of GST polymorphisms in white populations (20–45%) (31).…”

Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues

“…Our data indicate that neither inhibition of DNA methyltransferases, nor 1,3butadiene-induced genotoxic alterations, except in the lung of female mice, could explain the loss of cytosine DNA methylation in the liver and lung of C57BL/6J mice. This indicates that disruption of other molecular pathways such as mitochondrial dysfunction (Hartman et al 2017) and 1,3-butadiene-induced oxidative stress (Primavera et al 2008;Zhang et al 2015), known factors that cause cytosine DNA hypomethylation (Valinluck et al 2004), or alterations in one-carbon metabolism and tricarboxylic acid cycle, may cause loss of DNA methylation in the liver and lung of C57BL/6J mice.…”