Influence of glutathione S-transferases polymorphisms on biological monitoring of exposure to low doses of benzene

Carrieri, Mariella; Bartolucci, Giovanni Battista; Scapellato, Maria Luisa; Spatari, Giovanna; Sapienza, Daniela; Soleo, Leonardo; Lovreglio, Piero; Tranfo, Giovanna; Manno, Maurizio; Trevisan, Andrea

doi:10.1016/j.toxlet.2011.11.031

Cited by 30 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, the GSTT1 null genotype was found in multiple human studies to be a risk factor for both Hodgkin and non‐Hodgkin lymphoma . Consistent with these findings, GSTT1 detoxifies several environmental chemicals that have been linked to lymphoid cancers in humans …”

Section: Introductionsupporting

confidence: 54%

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Ginn

Sacco

Wong

et al. 2012

Vet Comparative Oncology

View full text Add to dashboard Cite

Glutathione-S-transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over-represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77-22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.

show abstract

Section: Introductionsupporting

confidence: 54%

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Ginn

Sacco

Wong

et al. 2012

Vet Comparative Oncology

View full text Add to dashboard Cite

show abstract

“…The occupational safety and health administration (OSHA), states that, CBCs should be monitored for workers exposed to benzene (OSHA 2012). Occupational exposures to benzene occur within the petrochemical plants, petroleum refineries (Edokpolo et al 2015), petrol distribution, and in manufacturing industries that require aromatic solvents or glues that contain benzene such as rubber production, shoe manufacturing, and printing (Weisel 2010; Carrieri et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity

et al. 2017

View full text Add to dashboard Cite

Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR–RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23–3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23–3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14–4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.

show abstract

“…The most consistent correlation between genotype and SPMA excretion has been observed for GSTT1 . Many but not all studies have demonstrated that the GSTT1 -null genotype results in lower levels of urinary SPMA, and thus less efficient detoxification of BO [15–18]. Fewer studies have shown a significant effect of the GSTM1 -null genotype [19–22].…”

Section: Introductionmentioning

confidence: 99%

Benzene oxide is a substrate for glutathione S-transferases

Zarth

Murphy

Hecht

2015

Chemico-Biological Interactions

View full text Add to dashboard Cite

Benzene is a known human carcinogen which must be activated to benzene oxide (BO) to exert its carcinogenic potential. BO can be detoxified in vivo by reaction with glutathione and excretion in the urine as S-phenylmercapturic acid. This process may be catalyzed by glutathione S-transferases (GSTs), but kinetic data for this reaction have not been published. Therefore, we incubated GSTA1, GSTT1, GSTM1, and GSTP1 with glutathione and BO and quantified the formation of S-phenylglutathione. Kinetic parameters were determined for GSTT1 and GSTP1. At 37 °C, the putative Km and Vmax values for GSTT1 were 420 µM and 450 fmol/s, respectively, while those for GSTP1 were 3600 µM and 3100 fmol/s. GSTA1 and GSTM1 did not exhibit sufficient activity for determination of kinetic parameters. We conclude that GSTT1 is a critical enzyme in the detoxification of BO and that GSTP1 may also play an important role, while GSTA1 and GSTM1 seem to be less important.

show abstract

Influence of glutathione S-transferases polymorphisms on biological monitoring of exposure to low doses of benzene

Cited by 30 publications

References 24 publications

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity

Benzene oxide is a substrate for glutathione S-transferases

Contact Info

Product

Resources

About