• Korean Journal of Environmental Biology
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• v.33 no.4
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• pp.450-458
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• 2015

The heat shock proteins (Hsps), one of the most highly conserved groups of proteins, play crucial roles in protecting cells against environmental stressors, such as temperature, salinity, heavy metals and pathogenic bacteria. The glutathione S-transferases (GST) have important role in detoxification of oxidative damage, environmental chemicals and environmental stress. The purpose of this study is to investigate the gene expression of Hsp70 and GST on change of temperature and salinity in Mytilus coruscus. The M. coruscus was cultured in incubator of separate temperature and salinity (8, 20, $30^{\circ}C{\times}20$‰, 25‰, 30‰) for 28 days. Ten individuals in each group were selected after each 14 and 28 days exposure. Results that the expression of Hsp70 mRNA was no significant changed in M. coruscus exposed to temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$) and salinity (20‰, 25‰, 30‰) for 14 days. Whereas the expression of Hsp70 mRNA was increased in exposure to temperature $30^{\circ}C$ and salinity (20‰, 25‰, 30‰) for 28 days. The expression of GST mRNA was increased in exposure to temperature $30^{\circ}C$, salinity (25‰, 30‰) for 14 days and temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$), salinity (20‰, 25‰, 30‰) for 28 days. These results suggest that Hsp70 and GST were played roles in biomarker gene on the thermal and salinity stress.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2221-2224
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• 2013

The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M & GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5647-5652
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• 2012

The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to inter-individual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4725-4732
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• 2012

Aim: The incidence of stomach cancer in Mizoram is highest in India. We have conducted a population based matched case-control study to identify environmental and genetic risk factors in this geographical area. Methods: A total of 102 histologically confirmed stomach cancer cases and 204 matched healthy population controls were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H. pylori infections were determined by ELISA. Results: Tobacco-smoking was found to be an important risk factor for high incidence of stomach cancer in Mizoram. Meiziol (local cigarette) smoking was a more important risk factor than other tobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel nut consumption synergistically increased the risk of stomach cancer. Polymorphisms of GSTM1 and GSTT1 genes were not found to be directly associated with stomach cancer in Mizoram. However, they appeared to be effect modifiers. Persons habituated with tobacco smoking and/or tuibur habit had increased risk of stomach cancer if they carried the GSTM1 null genotype and GSTT1 non-null genotype. Conclusion: Tobacco smoking, especially meiziol is the important risk factor for stomach cancer in Mizoram. GSTM1 and GSTT1 genes modify the effect of tobacco habits. This study is a first step in understanding the epidemiology of stomach cancer in Mizoram, India.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.65-70
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• 2004

Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.149-155
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• 2001

Eighty-one workers including 38 employees directly incinerating industry wastes were recruited from a company located in South Korea. To evaluate the association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as internal dose of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometic assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex PCR method. The GPA NN phenotype frequency was higher in occupationally exposed group (n=14, mean$\pm$S.D. 6.6$\pm$12.0 in 10/SUP 6/ erythrocyte cells) than in non-exposed group (n=22, 2.1$\pm$3.5). Similarly, the GPA(NO or NN) phenotype frequency was higher in exposed group (n=14, 9.7$\pm$17.3) than non-exposed group (n=22, 4.2$\pm$6.3). The above differences failed to reach statistical significance, but a significant increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels (Spearman's correlation: p=0.06 (NO), p=0.07 (NO or NN)). When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 present genotype (Spearmans correlation; r=0.50, p=0.02). These results suggest that the association between urinary 1-OHPG and GPA mutation is be modulated by the GSTM1 genotype.

• Toxicological Research
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• v.17
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• pp.251-256
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• 2001

The expression of phase II detoxifying enzymes is affected by a variety of compounds and the induction of the enzymes plays an essential role in chemoprevention. A variety of phytochemicals such as sulfur-containing chemoprotective agents (SCC) may trigger cellular signals and activate phase II gene expression through ARE activation. see induces glutathione S-transferases. Studies were conducted to investigate the role of mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3-kinase) in the induction of GST (e.g. rGSTA2) by sec. We also studied the MAP kinase pathway responsible for the GST expression by see and compared that with the pathway activated by oxidative stress as a result of sulfur amino acids deprivation (SAAD). see inhibited phosphorylation of ERK1/2 although the effect of see on JNK and p38 MAP kinase was minimal. Wortmannin and LY294002. PI3-kinase inhibitors. abolished the increases in rGSTA2 mRNA and protein levels by SCC. Deprivation of cystine and methionine caused oxidative stress in H4IIE cells. as evidenced by a decrease in the reduced glutathione and an increase in prooxidant production. Electrophoretic mobility shift assay revealed that the ARE complex consisting of Nrf-1/2 and Maf proteins was activated 12~48 h. The rGSTA2 mRNA and protein levels were increased by SAAD. Activation of ARE and induction of rGSTA2 were both completely inhibited by PI3-kinase inhibitors. Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. The results of this study showed that PI3-kinase might play an essential role in the ARE-mediated rGSTA2 induction by see or SAAD and that the dual MAP kinase pathways were responsible for the enzyme induction.

• The Plant Pathology Journal
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• v.24 no.4
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• pp.375-383
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• 2008

It is well known that NtMEK2, a tobacco MAPK kinase, is the upstream kinase of both salicylic acid-induced protein kinase and wound-induced protein kinase. In addition, expression of $NtMEK2^{DD}$, a constitutively active mutant of NtMEK2, is known to induce multiple defense responses in tobacco. In this study, transgenic rice plants that contained an active or inactive mutant of NtMEK2 under the control of a steroid inducible promoter were generated and used to determine if a similar MAPK cascade is involved in disease resistance in rice. The expression of $NtMEK2^{DD}$ in transgenic rice plants resulted in HR-like cell death. The observed cell death was preceded by the activation of endogenous rice 48-kDa MBP kinase, which is also activated by Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice. In addition, prolonged activation of the MAPK induced the generation of hydrogen peroxide and up-regulated the expression of defense-related genes including the pathogenesis-related genes, peroxidases and glutathione S-transferases. These results demonstrate that NtMEK2 is functionally replaceable with rice MAPK kinase in inducing the activation of the downstream MAPK, which in turn induces multiple defense responses in rice.

• Journal of fish pathology
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• v.33 no.1
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• pp.45-53
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• 2020

Doxycycline is a semi-synthetic broad-spectrum antibiotic, and it has been used to get rid of bacteria in animals and humans. The use of antibiotics has greatly contributed to the aquaculture production although its misuse sometimes presents public health problems. This study was performed to investigate the toxic effects of doxycycline on whiteleg shrimp (Litopenaeus vannamei) administered for possible infection treatments. The shrimp were allocated into four groups and doxycycline was fed three times a day for 7 days at 0, 20, 50 and 100 mg/kg to each group. After 24 hr following the 7-day treatment, hemolymph and hepatopancreas were used for blood and biochemical analysis: Total hemocyte counts, Total protein, Total cholesterol, Gluscose, Glutamic pyruvic transaminase, Glutamic oxaloacetic transaminase, Glutathione peroxidase, Superoxide dismutase, Glutathione-s-transferases, Total antioxidant capacity colorimetric and Acid phosphatase. In addition, histopathological examination was performed on the hepatopancreas and muscle. It was observed that body weight gain was significantly retarded in 100 mg/kg doxycycline group. Doxycycline was found to induce biochemical or functional disorders at 100 mg/kg as observed many of the blood and biochemical parameters were significantly reduced. In conclusion, it was judged that there will be no major toxicity problems with doxycycline when used for shrimp aquaculture at regular doses.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7187-7191
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• 2013

Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.