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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 11; pp. 3004 - 3012
• Main Authors: Primavera, Alessandra, Fustinoni, Silvia, Biroccio, Antonino, Ballerini, Sabrina, Urbani, Andrea, Bernardini, Sergio, Federici, Giorgio, Capucci, Enrico, Manno, Maurizio, Lo Bello, Mario
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-11-2008
• Subjects: 1,3-butadiene; Adult; Biomarkers - blood; Butadienes - toxicity; Case-Control Studies; Erythrocytes - enzymology; Female; Genotype; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - metabolism; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Glutathione transferases; glutathionylated hemoglobin; Hemoglobins - metabolism; Humans; Male; Occupational Exposure; Oxidative Stress; Petroleum; Polymerase Chain Reaction; Polymorphism, Genetic; Regression Analysis; Statistics, Nonparametric
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0443

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 μg/m 3 in 1,3-butadiene-exposed 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)