• Toxicological Research
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• 제7권2호
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• pp.191-208
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• 1991

Pulmonary conjugation pathways may be important for the metabolism of xenobiotics introduced via airways of systemically. The objective of this study was to determine the pulmonary conjugating capacity in both the isolated perfused rabbit lung (IPRL) and in vitro, and the ability of ethanol to alter the above. The IPRL was capable of conjugating glutathione (GSH) with either 1-chloro-2,4-dinitrobenzene (CDNB) of 1,2-epoxy-(p-nitrophenoxy) propane(ENP). The pulmonary GSH conjugation with ENP was inhibited by cibacron blue, indicating the presence of glutathione-S-transferase (GST) u and/or classes, but it was not altered by buthionine sulfoximine, a selective inhibitor of Gamma-glutamylcysteine synthetase.

• 대한수의학회지
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• 제32권4호
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• pp.649-661
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• 1992

This study was performed to compare DNA content by flow cytometer (FCM) and glutathione S-transferase placental form (GST-P) positive foci for searching objective and accurated properties of tumor. Sprague-Dawley rats aged six weeks were divided into three groups and group 1 and 2 of rats were given an intraperitoneal injection of diethylnitrosamine at 200mg/kg body weight and group 3 of rats were given saline. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. Group 1 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for six weeks, group 2 and 3 of rats were begun to feed on basal diets. At 4, 6, and 8 weeks after initiation, all groups of rats were killed, livers were extracted for H & E stain, immunohistochemical stain, and DNA ploidy analysis. In quantitative analysis for GST-P positive lesion number and area by using Image Analyzer, group 1 and 2 represented significant difference in comparison with group 3. In ploidy distribution, diploid cells of group 1 and 2 were increased significantly in comparison with those of group 3 at 4, 6, and 8 weeks after initiation, respectively tetraploid cells were reduced. But S-phase cells were not changed significantly. It is concluded that ploidy change by FCM is useful as objective data for early detection in hepatocarcinogenesis. Therefore, methodology and study of DNA content are carried out for more objective and accurate ploidy analysis in liver tumor.

• 한국어병학회지
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• 제32권2호
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• pp.113-121
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• 2019

Effects on glutathione-related antioxidant parameters were examined after a chronic exposure of olive flounder, Paralichthys olivaceus to dietary 4-tert-octylphenol (4-tert-OP). Fish were fed diets containing 4-tert-OP at 0, 1, 5 and 10 mg/kg diet for 6 weeks. Antioxidant parameters examined were reduced glutathione (GSH) contents and enzyme activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPx) in tissue homogenates of the liver, kidney and gill. It was observed that all parameters examined increased although there were some differences in dose responses and temporal patterns in the increase. GSH contents increased after exposure to 4-tert-OP in the three organs examined. However, the GSH increase was evident only after 4 weeks in the liver whereas it was elevated after 2 weeks in the kidney and gill. GR activity exhibited a significant increase in response to 4-tert-OP at 1 mg/kg in all three organs, however, its activity returned to control levels when exposed to 5 and 10 mg/kg. Hepatic GST activity showed an earlier increase at week 2 in contrast to the kidney and gill where they increased after 4 weeks of 4-tert-OP exposure. Temporal patterns in GPx activity changes to 4-tert-OP exposure were dissimilar among the organs: hepatic activity increased from week 2 through week 6; renal activity increased transiently at week 2; gill levels were higher through weeks 4 - 6. The results suggest that elevation of several GSH-related antioxidant parameters can be considered as evaluation criteria for 4-tert-OP-induced oxidative stress in a fish.

• 대한두경부종양학회지
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• 제18권2호
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• pp.150-156
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• 2002

Objectives: Most of human cancers may result from exposure to environmental carcinogens, and individual effectiveness in the detoxification of these chemicals will influence susceptibility to malignant disease. Glutathione S-Transferases(GSTs) enzymes are involved in the detoxification of active metabolites of many carcinogens from tobacco smoke and may be important in modulating susceptibility to smoke-related cancer. The purpose of this study is to determine the polymorphism of GSTM1, GSTT1, and GSTP1 in control group and head and neck squamous cell carcinoma group of Korean, and to investigate the effect of GSTs polymorphism on the risk of head and neck cancer. Materials and Methods: A hospital-based case-control study was performed with a group of 133 control individual and 136 head and neck squamous cell carcinoma patients. The polymorphisms of GSTs were analysed using polymerase chain reaction in GSTM1 and GSTTl, and polymerase chain reaction-restriction fragment length polymorphism in GSTP1. Results: The relative risk (odds ratio) of GSTM(-) genotype was 1.14(95% CI, 0.70-1.85) compared to GSTM1(+). The odds ratio of GSTTl(-) genotype was 0.91(95% CI, 0.55-1.50). In old age($65$) group, the odds ratio of GSTT1(-) genotype was 5.2(95% CI, 1.53-17.89). The GSTP1 Val/Val genotype conferred a 1.7-fold risk(95% CI, 0.40-7.34) of head and neck cancer compared with GSTP1 Ile/Ile genotype. Among the combined genotypes of GSTs, GSTM1(-)/GSTT1(+)/GSTP1 Val/Val and GSTM1(-)/GSTTl(-)/GSTP1 Ile/Val genotypes conferred a 2.6-fold and 1.3-fold risk(95% CI, 0.24-14.15 and 0.43-3.14) compared with the GSTM1(+)/GSTTl(+)/GSTP1 Ile/Ile genotype, respectively. Conclusion: Polymorphism of GSTs might modulate susceptibility to head and neck cancer in Korean population. The genotype of GSTP1 Val/Val and combined genotypes of GSTM1(-)/GSTT1(+)/GSTP1 Val/Val, and GSTM1(-)/GSTT1(-)/GSTP1 Ile/Val might be important risk factors to determine the individual susceptibility to head and neck squamous cell carcinoma.

• Korean Journal of Acupuncture
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• 제18권1호
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• pp.11-20
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• 2001

댑싸리하고초 약침액을 이용하여 phase II detoxification 효소인 quinone reductase (QR 및 GST) 유도, GSH 생성량, phase I 효소 cytochrome P4501A1 활성억제, 발암물질 B[a]P-DNA adduct 형성의 저해효과 등을 측정하였다. QR 생성 유도를 Hepa1c1c7로 실험한 결과, 댑싸리하고초 약침액및 열수추출액 모두에서 유도 되었으며, 농도가 높아질수록 유도율이 더 높게 나타났으며, GSH와 GST의 유도율도 약침액에서 나타났다. 댑싸리하고초 약침액 $5{\times}$에서 45.2%의 cytochrome P4501A1 효소활성 저해효과를 측정할 수 있었다. 또한 B[a]P-DNA binding 저해효과를 실험한 결과, 약침액 $3{\times}$ 농도에서 45.0%의 저해효과가 있었다. 이상의 결과에 의하면 댑싸리하고초 약침액은 암억제 물질로서의 기능을 충분히 발휘할 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제8권6호
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• pp.663-668
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• 1998

Several neurodegenerative diseases such as Huntington's disease, dentatorubralpallidoluysian atrophy, spinobulbar muscular atrophy, Machado-Joseph disease, and spinocerebellar ataxias type 1 are associated with the aggregation of expanded glutamine repeats within their proteins. Generally, in clinically affected individuals, the expansion of the polyglutamine sequences is beyond 40 residues. To address the length of polyglutamine that forms aggregation, we have constructed plasmids encoding glutathione S-transferase (GST) Machado-Joseph disease gene fusion proteins containing polyglutamine and investigated the formation of aggregates in E. coli. Surprisingly, even $(Gin)_8$, in the normal range as well as $(Gin)_{65}$ in the pathogenic range enhanced the formation of insoluble protein aggregates, whereas $(Ser)_8$, and $(Aia)_8$, did not form aggregates. Our results indicate that the formation of protein aggregates in GST-polyglutamine proteins is specifically mediated by the polyglutamine repeat sequence within their protein structure. Our study may contribute to the understanding of the molecular mechanism of the formation of protein aggregates in neurodegenerative disorders and the development of preventative strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3201-3205
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• 2014

The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions.

• 약학회지
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• 제36권2호
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• pp.180-187
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• 1992

This study investigated the hypothesis that carcinogen-induced elevation of oxyradical during the hepatocarcinogenesis in rat. The hepatic preneoplastic lesions in the Spraque-Dawley rats were induced by the carcinogen treatment such as diethylnitrosamine(DEN) and acetylaminofluorene(AAF) in combination with partial hepatectomy(PH). The liver sample was taken at 2, 6, 10 and 16 months after carcinogen treatments followed by PH. Carcinogen treatments initially increased the indices of oxidative damage(activities of xanthine oxidase and production rates of superoxide anion, microsomal hydrogen peroxide, hydroxyl radical) in the liver compared to PH groups. However, cytosolic hydrogen peroxide did not change significantly throughout the full time period. Of hydrogen peroxide scavenger, the catalase was remained lower than PH groups, whereas the peroxidase was increased after carcinogen treatments. Morphologically, the immunohistochemical analysis with glutathione-S-transferase of a placenta form(GSTP) antibody was used to detect the induction of preneoplastic nodules. During the hepatocarcinogenesis, both production rate of hydroxyl radical and activity of glutathione-S-transferase(GST) markedly increased with the appearance of the preneoplastic nodule. These results indicated that the hydroxyl radical of reactive oxygen species seemed to have a major influence on the hepatocarcinogenesis and the effect of time after removal of the carcinogen also appeared to be highly critical in the hepatocarcinogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권5호
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• pp.364-371
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• 2002

Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.

• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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• pp.55-61
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• 1998

Glutathione-S-transferases (GSTs) detoxify electrophilic xenobiotics and reactive metabolites. Recently benzene-fused heterocycles have been shown to increase the total amount of hepatic GSTs in rats. Primarily this study aimed to determine the induction of GSTs by benzoazoles (BAs) including benzoxazole (BX), 2-methylbenzoxazole (M-BX), 2,5-dimethyl benzoxazole (D-BX), benzothiazole (BT), aminobenzothiazole (A-BT) and 2-mercaptobenzothiazole (M-BT) in rats. Hepatic cytosol and poly(A)$^+$ mRNA were prepared from rats after oral administration of BX, BT, M-BX, D-BX, A-BT and M-BT for 5 consecutive days at doses of 1 mmol/kg. Western immunoblot and northern blot analysis were conducted with rabbit anti-GST Ya, Yb$_1$, Yb$_2$, Yc antibodies and cDNA probes containing = 500 bps in the specific coding regions of Ya, Yb$_1$, Yb$_2$, Yc$_1$, and Yc$_2$, respectively. All BAs increased the amount of enzymes and mRNA levels of GSTs. BT was the most effective inducer of GSTs among the compounds examined in this study. Although A-BT and M-BT, the derivatives of BT, induced GSTs, these chemicals had lesser effect on induction of GSTs than BT. The derivatives of BX also induced less GSTs than the parent compound and the addition of methyl group to the benzene ring of BX reduced the induction of GSTs. BAs had better inductive effects on the class $\alpha$(Ya, Yc) than class $\mu$ GSTs (Yb$_1$, Yb$_2$). BAs enhanced mRNA levels of GSTs in parallel with the protein levels. These results indicate that 1) most of BAs induced various isozymes of GSTs, 2) the induction of GSTs appears to be correlated with the chemical structure of the derivatives, and 3) the expression of GST by BAs is presumably under the transcriptional regulation.