Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case-control study was carried out to examine the relation between genetic polymorphisms of five genes, cigarette smoking and colorectal cancer risk. We collected blood samples from 106 colorectal cancer patients and 100 healthy persons, then analyzed them to identify genotypes for glutathione S-transferase (GST) M1, T1, P1, N-acetyltransferase (NAT) 1 and 2 by the PCR method. We also collected smoking history data from all participants by questionnaire. From statistical evaluation on various combinations of genotypes, we observed that the cancer risk of those who have both GSTM1 present genotype and GSTP1 Adenine/Adenine homozygous genotype was significantly less than those who have other combinations of genotypes for two genes. For other combinations of genes, there was no significant association between genotype and cancer risk. There was also no significant association between amount of cigarette smoking and the cancer risk. These findings suggest that it is valuable to study cancer risk when examining genotypes of more than two genes at the same time. For further study, we need to collect more samples to increase statistical reliability, and besides cigarette smoking, include the nutrition data as an environmental factor.
 ...
PMID:Glutathione S-transferase (GST) M1, T1, P1, N-acetyltransferase (NAT) 1 and 2 genetic polymorphisms and susceptibility to colorectal cancer. 1043 61

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.
 ...
PMID:Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. 1047 Oct 65

A nomenclature system for all human metabolic gene polymorphisms is suggested. This system should replace the various nomenclatures used in the literature to describe polymorphisms in many of the cytochrome P450 (CYP) genes, as well as the glutathione S-transferase (GST) and N-acetyltransferase (NAT) genes. The system is based on two published papers proposing nomenclatures for the various alleles of CYP2D6 and NAT. The gene name is followed by an asterisk, followed by an arabic number designating the specific polymorphism in chronological order of first publication. The final number may be followed by letters A,B, etc. when allelic subtypes exist. A table is presented showing nomenclature for 72 polymorphisms in 12 genes, including detailed descriptions and commonly used previous designations.
 ...
PMID:A nomenclature system for metabolic gene polymorphisms. 1049 44

In order to avoid the accumulation of harmful xenobiotics in cells, living organisms have developed ways for their elimination. Multiple xenobiotic metabolizing enzymes with variable but partially overlapping catalytic properties play a key role in the elimination process. These enzymes are encoded by superfamilies of genes which, during the course of evolution, have evolved in a way that has made it possible for the different species to survive and take advantage of different habitats and diet containing a variable composition of harmful xenobiotics. As a result of this evolutionary process, species have achieved capacities to metabolize xenobiotics which are appropriate for their survival but which may differ considerably from those of other species. This evolutionary process may also explain the interethnic and interindividual variability of drug metabolism in humans. Because many carcinogens are substrates of drug-metabolizing enzymes it is reasonable to assume that humans have a variable capacity to activate or inactivate carcinogens. This has been shown to be the case. It appears that most of the carcinogen-metabolizing enzymes are inducible by xenobiotics: they respond to environmental stimuli and therefore vary in their activity. Furthermore, many of the encoding genes are polymorphic and multiple allelic variants relevant for the phenotype may exist in human populations. Analysis of the genetic variability that affects the capacity to metabolize carcinogens in humans has shown that a few members of the cytochrome P450, glutathione S-transferase and N-acetyltransferase gene families may play an Important role in chemical carcinogenesis. Yet for several enzymes such a role has not been established until now, although their catalytic properties and expression in human tissues suggest that such a role should exist. More studies on the role of individual enzymes in chemical carcinogenesis are therefore warranted.
 ...
PMID:Metabolism of xenobiotics and chemical carcinogenesis. 1049 45

Paper provides a survey of the basic knowledge on the genetic polymorphism of enzymes involved in the metabolism of medicinal drugs and other xenobiotics. The major implications of this phenomenon have been described, namely the interindividual variability in the therapeutic effect of drugs differently metabolised by the polymorphically determined enzymes, or the interindividual variability in the susceptibility to neoplastic processes related to the polymorphically determined enzymes metabolising xenobiotics. Recent advances in the understanding of the molecular genetics of enzymes metabolising drugs and other xenobiotics (particularly cytochrome P-450, glutathione S-transferase, N-acetyltransferase, UDP-glucoronosyltransferases and others), help to understand the molecular basis of several genetic polymorphisms. Present article reviews the current status of studies on polymorphism of xenobiotics-metabolising enzymes and brings a discussion to their pharmacotherapeutical relevance and to their significance for identification of susceptible individuals/subgroups in the carcinogen exposed population.
 ...
PMID:[Pharmacologic and toxicologic results in genetic polymorphisms (review)]. 1053 75

Biotransformation plays an important role in the carcinogenic activity and organ specificity of environmental carcinogens. Large interindividual variation in the biotransformation has been reported, and genetic polymorphisms in some xenobiotica metabolizing enzymes can in part explain some of these differences. The concentration of the ultimate carcinogen, that will react with DNA, is determined by the rate of activation and detoxification. Individuals with a decreased rate of detoxification, i.e., lacking the glutathione S-transferase M1 gene, have a slightly higher level of bulky carcinogen-DNA adduct in some tissues, and do also have an increased level of chromosomal aberrations. In addition, the genotype may also influence the type of mutations, e.g., in tumor suppressor gene, transversion being predominant in the GSTM1 null group. People with slow N-acetyltransferase activity do generally have a higher adduct level of aromatic amines in bladder tissues. Genetic polymorphism in either CYP1A1 or glutathione S-transferase is linked to an increased risk of smoking related cancers, while N-acetyltransferase activity is related to cancers in which aromatic amines are the main risk factor. Combination of the high risk genotypes for activating and detoxification enzymes, e.g., CYP1A MspI/GSTM1 null is not only associated with an increased risk of cancer development, but also an increased level of markers of the biological active dose and early markers of effect. Additional studies on the role of genetic variants of xenobiotica metabolizing enzymes and combinations thereof at relevant low levels of exposure are important in order to establish guidance values for toxic compounds.
 ...
PMID:Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response. 1063 78

Polymorphism and the induction/inhibition of drug-metabolizing enzymes, such as cytochrome P450, aldehyde dehydrogenase (ALDH), glutathione S-transferase (GST), N-acetyltransferase (NAT), and NAD(P)H-quinone oxidoreductase (NQO1), were reviewed in relation to susceptibility to disease and to inter-individual difference in biological monitorings. A number of genetic and acquired factors can influence the susceptibility of an individual to chemicals, creating a so-called predisposition. Most cases in which genetic factors were present resulted from polymorphism of drug-metabolizing enzymes. However, conflicting reports have appeared on the relationship between polymorphism and risk of disease; in some cases, biologically plausible mechanisms linking genotypes and disease are not yet in evidence. Current findings based on biological monitoring of chemicals are insufficient to evaluate the relationship between genetic polymorphism and acquired risk when exposure has occurred in an occupational area. Investigation of such situations has generated data implicating GSTT1, GSTM1, NAT2, and NQO1 polymorphisms in biological monitoring of some chemicals; the ALDH2 polymorphism is the likely link between the genotype and the metabolism of low molecular aliphatic aldehydes. Although this polymorphism is limited in the case of Japanese as well as other Asian subjects, the inhibitors of ALDH2 activity such as trichloroethylene may produce a false polymorphism of this gene. As to the effect of factors influencing acquired predisposition, such as ethanol intake, intake of low carbohydrate diet or diabetes, corroborative epidemiological studies may be further required.
 ...
PMID:Polymorphism of drug-metabolizing enzymes in relation to individual susceptibility to industrial chemicals. 1081 37

The effect of propofol on the hepatic and extrahepatic conjugation enzyme systems was assessed in vitro using microsomal and cytosolic preparations of human liver, hamster kidney, lung and gut. The functional activities of phase-II enzymes, including uridine diphosphate-glucuronosyltransferase (UDPGT), glutathione S-transferase (GST) and N-acetyltransferase (NAT) were evaluated in the presence of various concentrations of propofol (0.05-1.0 mmol litre-1), using 1-naphthol, 1-chloro-2,4-dinitrobenzene and p-aminobenzoic acid as substrates respectively. Propofol produced concentration-dependent inhibition of UDPGT activity in human liver microsomes. Propofol did not produce significant inhibition of human hepatic GST activity at concentrations below 1.0 mmol litre-1. In contrast, NAT activity was unaffected by propofol 0.05-1.0 mmol litre-1 in human liver cytosolic preparations. In extrahepatic tissues, hamster renal and intestinal UDPGT activities were significantly inhibited by propofol at 0.25-1.0 mmol litre-1. In these tissues, GST and NAT were unaffected by propofol at 1.0 mmol litre-1. Propofol produced differential inhibition of human liver and hamster extrahepatic conjugation enzymes as a result of different substrate and tissue specificities. The potential interference of the metabolic profile of phase-II enzymes as a result of inhibition by propofol (especially of UDPGT and GST) should be considered when using propofol with other drugs for anaesthesia.
 ...
PMID:Effects of propofol on functional activities of hepatic and extrahepatic conjugation enzyme systems. 1089 55

The present study has determined the effects of 6-nitrochrysene (6-NC) on human cytochrome P450-dependent monooxygenases in human hepatoma HepG2 cells. Treatment of HepG2 cells with 6-NC increased the activities of microsomal benzo[a]pyrene hydroxylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylases, cytosolic glutathione S-transferase and N-acetyltransferase, and S9 metabolic activation of 6-NC in the Ames mutagenicity test. Immunoblot and RNA blot analyses revealed that 6-NC induced CYP1A1 protein and mRNA levels in the hepatoma cells. Nuclear transcription assay demonstrated that 6-NC increased the transcription rate of CYP1A1 gene in HepG2 cells. Treatment of human lung carcinoma NCI-H322 cells with 6-NC increased benzo[a]pyrene hydroxylase activity and CYP1A1 protein and mRNA levels. These results demonstrate that 6-NC is an inducer of human CYP1A1 and the induction occurs at a transcriptional level in HepG2 cells. The ability of 6-NC to induce liver and lung CYP1A1 may be an important factor to consider in assessing 6-NC metabolism and toxicity in humans.
 ...
PMID:Induction of cytochrome P450 1A1 in human hepatoma HepG2 cells by 6-nitrochrysene. 1103 35

Inter-individual variability in carcinogen metabolism has been attributed in part to the polymorphic expression of several phase I and II detoxification enzymes. The role of these genetic polymorphisms in cancer susceptibility has been most extensively evaluated for isozymes of cytochrome P450 (CYP1A1, CYP2D6, and CYP2E1), N-acetyltransferase (NAT1 and NAT2), glutathione S-transferase (GSTM1, GSTT1, and GSTP1), microsomal epoxide hydrolase, and NAD(P)H:quinone oxidoreductase. Our understanding of the genetic basis of cancer risk has been enhanced most recently by establishment of genotype-phenotype correlations in humans and identification of numerous diverse factors, both genetic and environmental, that can modify risk.
 ...
PMID:Genetic polymorphism and cancer risk. 1112 50


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