Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics-metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females.
...
PMID:Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms. 1002 76

Recently, we examined normal human pancreas tissue for DNA adducts derived from either exogenous chemical exposure and/or endogenous agents. In an effort to explain the different types and levels of DNA adducts formed in the context of individual susceptibility to cancer, we have focused on gene-environment interactions. Here, we report on the levels of hydrophobic aromatic amines (AAs), specifically those derived from 4-aminobiphenyl (ABP), and DNA adducts associated with oxidative stress in human pancreas. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been performed. Using the same DNA, the genotypes were determined for N-acetyltransferase 1 (NAT1), the glutathione S-transferase (GST) M1, GSTP1, GSTT1, and NAD(P)H quinone reductase-1 (NQO1) as possible modulators of adduct levels because their gene products are involved in the detoxification of AAs, lipid peroxidation products and in redox cycling. These results indicate that ABP-DNA adducts, malondialdehyde-DNA adducts, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) adducts are present at similar levels. Of the metabolic genotypes examined, the presence of ABP-DNA adducts was strongly associated with the putative slow NAT1*4/*4 genotype, suggesting a role for this pathway in ABP detoxification.
...
PMID:Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype. 1006 66

Several polymorphic glutathione S-transferase enzymes are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and may therefore be important in modulating susceptibility to smoking-related cancers. As part of a hospital-based case-control study performed in France among Caucasian smokers, we studied GSTM1, GSTM3, GSTP1 and GSTT1 gene polymorphisms in 121 patients with oral cavity and pharyngeal cancers and 172 hospital controls using peripheral blood DNA. An increase in risk was found among carriers of the GSTP1 (AG or GG) genotype (OR 1.6, 95% CI 1.0-2.8, p = 0.07) or the GSTT1 null genotype (OR 2.0, 95% CI 1.0-4.0, p = 0.05). The effect of these at-risk genotypes was most marked in subjects with a history of more than 30 years of smoking, among whom the respective ORs were 2.0 (95% CI 1.0-3.9) and 3.3 (95% CI 1.3-8.1), though the interaction tests between these genotypes and duration of smoking were not significant. In contrast, neither the GSTM1 null genotype nor the GSTM3 AA genotype was associated with oropharyngeal cancer risk (OR 0.9, 95% CI 0.5-1.5 and OR = 1.3, 95% CI 0.7-2.3, respectively). Our results thus suggest that GSTP1 and GSTT1 gene polymorphisms modulate susceptibility to smoking-related cancers of the oral cavity and pharynx.
...
PMID:Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers. 1007 51

The glutathione S-transferases (GSTs) are involved in the metabolism of numerous potential prostate carcinogens. Common homozygous germ-line deletions exist in the genes that encode GST-mu (GSTM1) and GST-theta (GSTT1) and preclude enzyme expression. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 237 incident CaP cases and 239 age- and race-matched controls. The probability of having CaP was increased in men who had nondeleted (functional) genotypes at GSTT1 (odds ratio, 1.83; 95% confidence interval, 1.19-2.80) but not GSTM1 (odds ratio, 1.07; 95% confidence interval, 0.74-1.55). No interaction of these genes in CaP etiology was observed. GST-theta is highly expressed in the prostate and can produce genotoxic effects upon exposure to specific carcinogens. These results suggest that GSTT1 is associated with CaP risk.
...
PMID:Glutathione S-transferase-mu (GSTM1) and -theta (GSTT1) genotypes in the etiology of prostate cancer. 1020 29

Polymorphisms in glutathione S-transferase (GSTs) may predispose to colorectal cancer through deficient detoxification of environmental carcinogens, although previous results are conflicting. A study with 178 matched case-control pairs was conducted to determine the effect of the GSTT1 and GSTM1 null genotypes and polymorphisms in GSTP1 on colorectal cancer susceptibility. In a secondary analysis, we examined interactions between genotypes and with the N-acetyltransferase 2 (NAT2) genotype. Heterogeneity by age, sex, site, and stage of cancer was also examined. No effect of any genotype for GSTM1, GSTT1, or GSTP1 on colorectal cancer susceptibility was detected. Secondary end points showed that individuals with both the GSTT1 null and NAT2 slow genotypes combined appeared to be at increased risk of colorectal cancer (odds ratio = 2.33; 95% confidence interval, 1.1-5.0). We conclude that GST polymorphisms alone do not predispose to colorectal cancer in northeast England. We also observed possible effects of the GSTT1 null genotype on the age and stage at presentation, and these, together with the findings of an apparent interaction with NAT2 genotypes, need to be confirmed in further studies.
...
PMID:Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. 1020 30

1. Correlations between deletions in two glutathione S-transferase (GST) genes, GSTM1 and GSTT1 and susceptibility to Alzheimer's disease (AD), motor neuron disease (MND) and Parkinson's disease (PD) have been investigated by PCR, using primers specific for both genes. 2. It was found that males with a deletion of the GSTM1 gene were more susceptible to PD and males with a deletion of the GSTT1 gene more susceptible to MND and PD, possibly implying that environmental factors which specifically target men may be involved. Furthermore, subjects with a deletion of the GSTT1 gene were more susceptible to AD.
...
PMID:Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease. 1021 3

To examine the association between genetic polymorphisms of glutathione S-transferase (GST) M1 and T1 and susceptibility to esophageal cancer, a multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from surgically removed esophageal tissues or scraped esophageal cells from cases with cancer (n = 45), cases with severe hyperplasia (n = 45), and sex/age matched normal controls (n = 45) from a high risk area, Linxian, China. Results showed that the frequency of the GSTM1-null genotype in cancer cases (44.4%) or hyperplasia cases (44.4%) was not significantly different from that in controls (46.7%). Similarly, no statistically significant differences were observed in the frequency of GSTT1-null genotype in cancer cases (40.0%) or hyperplasia cases (37.8%) when compared with the controlled population (51.1%). However, the frequency of combined GSTM1-nonnull and GSTT1-nonnull genotypes in cases with cancer (40.0%) and cases with hyperplasia (37.8%) showed a significant increase compared to that in controls (22.2%). Persons with both GSTM1 and GSTT1 positive genotypes had 4-fold risk in developing esophageal cancer (odds ratio, OR = 4.20; 95% confidence interval, CI = 1.23-14.36) and 2.6-fold risk for hyperplasia (OR = 2.64; 95% CI = 0.84-8.30), respectively. These results suggest that combined GSTM1-nonnull and GSTT1-nonnull genotypes may act as risk factor in the development of esophageal cancer in Linxian population.
...
PMID:[Glutathione S-transferase M1, T1 genotypes and the risk of esophageal cancer: a case-control study]. 1032 69

The kinetic properties of bacterial and rat liver glutathione S-transferases (GST) active with dichloromethane (DCM) were compared. The theta class glutathione S-transferase (rGSTTI-1) from rat liver had an affinity for dihalomethanes lower by three orders of magnitude (K(app) > 50 mM) than the bacterial DCM dehalogenase/GST from Methylophilus sp. DM11. Unlike the bacterial DCM dehalogenase, the rat enzyme was unable to support growth of the dehalogenase minus Methylobacterium sp. DM4-2cr mutant with DCM. Moreover, the presence of DCM inhibited growth with methanol of the DM4-2cr transconjugant expressing the rat liver GSTT1-1. In Salmonella typhimurium TA1535, expression of rat and bacterial DCM-active GST from a plasmid in the presence of DCM yielded up to 5.3 times more reversions to histidine prototrophy in the transconjugant expressing the rat enzyme. Under the same conditions, however, GST-mediated conversion of DCM to formaldehyde was lower in cell-free extracts of the transconjugant expressing the rat GSTT1 than in the corresponding strain expressing the bacterial DCM dehalogenase. This provided new evidence that formaldehyde was not the main toxicant associated with GST-mediated DCM conversion, and indicated that an intermediate in the transformation of DCM by GST, presumably S-chloromethylglutathione, was responsible for the observed effects. The marked differences in substrate affinity of rat and bacterial DCM-active GST, as well as in the toxicity and genotoxicity associated with expression of these enzymes in bacteria, suggest that bacterial DCM dehalogenases/GST have evolved to minimise the toxic effects associated with glutathione-mediated catalysis of DCM conversion.
...
PMID:Enzyme-mediated dichloromethane toxicity and mutagenicity of bacterial and mammalian dichloromethane-active glutathione S-transferases. 1035 Jan 86

The M1 member of the mu class of the glutathione S-transferase (GSTM1) gene is present in about 50% of individuals. GSTT1, a member of the theta class, which has been recently shown to be polymorphic, is expressed in 35-90% of individuals. In this study, 145 Japanese patients with urothelial transitional cell carcinoma and 145 healthy controls, frequency-matched for age and gender, were compared for frequencies of GSTM1 and GSTT1 genotypes. The urothelial cancer risk increased due to the GSTM1 null genotype (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.05-2.79). On the other hand, the OR tended to decrease due to the GSTT1 null genotype, although not significantly. Among individuals of the GSTM1 null genotype, those of the GSTT1-positive genotype had a two-fold risk (OR 2.62, 95% CI 1.36-5.05) compared with the GSTT1 null genotype (OR 1.25, 95% CI 0.62-2.51). A significant interaction between the GSTM1 genotype and smoking status was found; the GSTM1 null genotype was associated with an increased risk of urothelial cancer among smokers (OR 1.98, 95% CI 1.10-3.57).
...
PMID:Effects of glutathione S-transferase (GST) M1 and GSTT1 genotypes on urothelial cancer risk. 1039 66

Fifty-nine persons with industrial handling of low levels of acrylonitrile (AN) were studied. As part of a medical surveillance programme an extended haemoglobin adduct monitoring [N-(cyanoethyl)valine, CEV; N-(methyl)valine. MV: N-(hydroxyethyl)valine, HEV] was performed. Moreover, the genetic states of the polymorphic glutathione transferases GSTM1 and GSTT1 were assayed by polymerase chain reaction (PCR). Repetitive analyses of CEV and MV in subsequent years resulted in comparable values (means, 59.8 and 70.3 microg CEV/1 blood; 6.7 and 6.7 microg MV/1 blood). Hence, the industrial AN exposures were well below current official standards. Monitoring the haemoglobin adduct CEV appears as a suitable means of biomonitoring and medical surveillance under such exposure conditions. There was also no apparent correlation between the CEV and HEV or CEV and MV adduct levels. The MV and HEV values observed represented background levels, which apparently are not related to any occupational chemical exposure. There was no consistent effect of the genetic GSTM1 or GSTT1 state on CEV adduct levels induced by acrylonitrile exposure. Therefore, neither GSTM1 nor GSTT1 appears as a major AN metabolizing isoenzyme in humans. The low and physiological background levels of MV were also not influenced by the genetic GSTM1 state, but the MV adduct levels tended to be higher in GSTT1- individuals compared to GSTT1 + persons. With respect to the background levels of HEV adducts observed, there was no major influence of the GSTM1 state, but GST- individuals displayed adduct levels that were about 1/3 higher than those of GSTT1 + individuals. The coincidence with known differences in rates of background sister chromatid exchange between GSTT1- and GSTT1 + persons suggests that the lower ethylene oxide (EO) detoxification rate in GSTT1- persons, indicated by elevated blood protein hydroxyethyl adduct levels, leads to an increased genotoxic effect of the physiological EO background.
...
PMID:Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1. 1046 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---