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

Progress over the past 30 years has revealed many strengths of the rainbow trout as an alternative model for environmental carcinogenesis research. These include low rearing costs, an early life-stage ultrasensitive bioassay, sensitivity to many classes of carcinogen, a well-described tumor pathology, responsiveness to tumor promoters and inhibitors, and a mechanistically informative nonmammalian comparative status. Low-cost husbandry, for example, has permitted statistically challenging tumor study designs with up to 10,000 trout to investigate the quantitative interrelationships among carcinogen dose, anticarcinogen dose, DNA adduct formation, and final tumor outcome. The basic elements of the trout carcinogen bioassay include multiple exposure routes, carcinogen response, husbandry requirements, and pathology. The principal known neoplasms occur in liver (mixed hepatocellular/cholangiocellular adenoma and carcinoma, hepatocellular carcinoma), kidney (nephroblastoma), swim bladder (adenopapilloma), and stomach (adenopapilloma). Trout possess a complex but incompletely characterized array of cytochromes P450, transferases, and other enzymic systems for phase I and phase II procarcinogen metabolism. In general, trout exhibit only limited capacity for DNA repair, especially for removal of bulky DNA adducts. This factor, together with a high capacity for P450 bioactivation and negligible glutathione transferase-mediated detoxication of the epoxide, accounts for the exceptional sensitivity of trout to aflatoxin B1 carcinogenesis. At the gene level, all trout tumors except nephroblastoma exhibit variable and often high incidences of oncogenic Ki-ras gene mutations. Mutations in the trout p53 tumor suppressor gene have yet to be described. There are many aspects of the trout model, especially the lack of complete organ homology, that limit its application as a surrogate for human cancer research. Within these limitations, however, it is apparent that trout and other fish models can serve as highly useful adjuncts to conventional rodent models in the study of environmental carcinogenesis and its modulation. For some problems, fish models can provide wholly unique approaches.
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PMID:Fish models for environmental carcinogenesis: the rainbow trout. 872 7

In rodents, overexpression of glutathione S-transferase pi is a characteristic feature of foci of cellular alteration (FCA) and neoplastic liver lesions induced by genotoxic chemicals. Alterations of glutathione S-transferase (GST) expression in hepatic lesions have also been reported in fish exposed to environmental carcinogens, and cellular GST expression may be an important determinant of growth and progression of chemical-associated liver tumors in certain fish species. In the present study, GST expression was examined in hepatic lesions of brown bullheads (n = 44) from the Cuyahoga River, a highly industrialized site located in Cleveland, Ohio. GST proteins were detected by immunohistochemistry and polyclonal antibodies that recognize either two major bullhead GST proteins or a pi-like GST isoform. Hepatic lesions were present in 70% of the fish and included biliary hyperplasia and biliary fibrosis; eosinophilic, basophilic, clear cell, and vacuolated FCA; and biliary neoplasms. Eosinophilic FCA and biliary tumors were the most prevalent preneoplastic and neoplastic lesions. GST expression in hyperplastic biliary tissue, FCA and tumors did not markedly differ from that of surrounding normal hepatocytes or biliary epithelium. Some hepatocytes within eosinophilic FCA had decreased GST expression. A complete absence of GST immunoreactive protein was not observed in any lesion, and there were no marked differences when comparing GST pi to overall GST expression. Our results indicate that GST expression in hepatic lesions of brown bullhead exposed to environmental carcinogens does not significantly differ from that in surrounding normal cells and is therefore not a useful predictor of environmental carcinogenesis in this species. Furthermore, the regulation and expression of GST pi in bullhead hepatocarcinogenesis appears to differ markedly from that during hepatocarcinogenesis in rats and some other fish species.
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PMID:Glutathione S-transferase expression in pollution-associated hepatic lesions of brown bullheads (Ameiurus nebulosus) from the Cuyahoga River, Cleveland, Ohio. 1507 Nov 71

The skin acts as the first defence barrier against external environmental pollutants, including chemicals and UV radiation. Cytochrome P450 CYP1A1 and glutathione S-transferases (GSTs) found in melanocytes and skin basal layers were shown to participate both in the metabolism of xenobiotics and in detoxification of reactive oxygen species (ROS). In our study we analysed the distribution of single and combined CYP1A1, GSTM1, GSTT1 and GSTP1 genotypes contributing to inter-individual differences in metabolism of xenobiotics and ROS in 125 Slovenian healthy individuals and in 140 patients with sporadic malignant melanoma. Our results showed no statistically significant differences between melanoma patients and healthy controls in the frequency of polymorphic CYP1A1 and GST genotypes. The risk of developing melanoma was not significantly increased in individuals homo- or heterozygous for the CYP1A1*2A allele combined with GSTM1*0 genotype (OR: 1.86; 95% CI: 0.36-7.71), but increased slightly in carriers of CYP1A1*2A combined with both GSTM1*0 and GSTT1*0 genotypes (OR: 3.42; 95% CI: 0.36-29.6). Our results indicate that factors other than the polymorphic genes coding xenobiotic metabolising enzymes play a major role in protection against environmental carcinogenesis in human skin.
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PMID:Genetic susceptibility to environmental carcinogenesis in Slovenian melanoma patients. 1699 6