• Journal of Environmental Health Sciences
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• v.19 no.2
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• pp.69-77
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• 1993

In the present study, the comparison of liver damage in carbon tetrachloride (CCl$_4$)-treated rats with that those pretreated with ethanol and an effect of liver injury on the serum and liver xanthine oxidase (XOD) activity were evaluated. The increasing rate of liver weight per body wt., the levels of serum alanine aminotransferase, and the decreasing rate of hepatic glucose-6-phosphatase activity and the protein contents in the liver cell were higher in carbon tetrachloride-treated animals pretreated with ethanol than the carbon tetrachloride-treated group. Especially, the histopathological findings also showed more severe liver damage in the ethanol-pretreated rats than the rats treated with carbon tetrachloride only. In such a experimental condition the xanthine oxidase activity of serum and liver both of carbon tetrachloride-treated rats and those pretreated with ethanol were higher than that of each control group. And the increasing rate of xanthine oxidase enzyme activity to the control group was higher in carbon tetrachloride-treated group pretreated with ethanol than those treated with CCl$_4$. In addition, the heptic uricase activity and the serum levels of uric acid were more increased in carbon tetrachloride-treated group pretreated with ethanol than those in the CCl$_4$-treated rats. On the other hand, there were no statistical differences in hepatic catalase and glutathione S-transferase activities between the CCl$_4$-treated rats and those pretreated with ethanol. In conclusion, it is assumed that the more severe liver damage in ethanol pretreated rats would be due to oxygen free radical produced by the xanthine oxidase system.

• Bulletin of Food Technology
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• v.12 no.2
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• pp.26-38
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• 1999

조리가공 중 생성되는 주요 발암성 이환방향족아민(heterocyclic aromatic amine)인 Trp-P-1 및 Trp-P-2가 human 및 rat keratinocytes에 대해 나타내는 세포 독성을 colony expansion법의 의해 조사, 비교하였다. 특히 Trp-P-2는 human keratinocytes에 대해서는 독성을 나타내지 않은데 반해 rat keratinocytes(계대수 2-5)에 대해서는 독성을 나타내는 선택성을 나타내었다. 이러한 Trp-P-2의 종(species)간 독성감수성 차이가 대사 효소계 활성이나 mutagenic activation상의 차이에 기인되는지를 살펴본 결과, CYP4501As 및 독성감수성 차이가 크게 나타났던 human 및 rat keratinocytes의 microsome에서 거의 같았다. 이와 같은 결과는 CYP4501A1 및 CYP1B1의 mRNA의 발현정도를 northernblot에 의해 살펴보았던 결과에서도 일치하였다. 반면 Trp-P-2의 대사활성화 및 해독화에 관여하는 효소인 N.O-acetyltransferase(NAT)활성은 rat keratinocytes보다 human keratinocytes에서 높았다. 일반적으로 독성물질의 해독화에 관여하는 glutathione S-transferase(GST) 또한 rat keratinocytes보다 human keratinocytes에서 높게 나타났다. Trp-P-2가 mutagenic metabolite로 활성화되는 정도를 salmonella microsome microsuspension assay로 살펴본 결과, 독성 감수성 차이가 크게 나타났던 human 및 rat keratinocytes간의 활성은 비슷한 것으로 나타났다. DNA 및 단백질 adduct형성능의 경우, human 및 rat keratinocytes간 DNA adduct형성능에는 차이가 없었고, 단백질 adduct형성능의 경우만 Trp-P-2에 대한 독성감수성 정도가 컸던 rat keratinocytes가 다른 세포들에 비해 크게 나타났다. 이상의 결과를 종합해 볼 때, CYP1A- 또는 CYP1B1-관련 마이크로솜 효소활성이나 mutagenic activation은 human 및 rat keratinocytes간에 나타났던 독성 감수성의 차이를 설명할 수 없으며, 해독화에 관여하는 효소활성이 종간 관찰되었던 독성 감수성의 차이에 더 중요한 역할을 하는 것으로 보인다.

• Toxicological Research
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• v.18 no.3
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• pp.293-300
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• 2002

Chemical carcinogen-induced alteration of aldehyde metabolic enzymes were examined in clone 9 cell. Diethylnitrosamine (DENA), N-nitrosoethylurea (NEU) and N-nitrosomorpholine (NNM) were wed as model carcinogens. Changes in enzyme activities by repetitive treatment of DENA, NEU or NNM were analyzed in terms of specific activities and activity stainings of the enzymes on the gel. Upon treatment of DENA, lipid peroxide level increased upto 10 fold, indicating strong oxidative stress state of the cell. Notable enhancement of ADH and ALDH activity occurred after DENA treatment, while glutathione-S-transferase activity was slightly increased. Furthermore, about 2.5 fold higher superoxide dismutase (SOD) activity was detected during deactivation of catalase (CAT) activity by repetitive treatment of DENA. However in NEU-treated cell, about 2.3 fold higher ALDH activity was found while ADH activity was slightly increased. Notable increase CAT and SOD could also be found. In contrast, maximum 3.5 fold higher CAT activity occurred during SOD deactivation in NNM-treated cell. These results suggest that there might be different enzymatic responses in relation to cell protection against DENA, NEU or NNM.

• Journal of fish pathology
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• v.27 no.1
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• pp.11-16
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• 2014

The resistance against white spot syndrome virus (WSSV) infection in wild marine crab Gaetice depressus by the immunization of a recombinant glutathione-S-transferase (GST) fused VP28 protein (GST-VP28) was evaluated. The cumulative mortalities of GST-VP28 injected groups were lower than those of the control groups at 10 days of post-challenge, and the time to death of 50% crab ($TD_{50}$) was delayed by the immunization using GST-VP28. The group boosted with GST-VP28 after 2 weeks of primary immunization clearly showed longer $TD_{50}$ than non-boosted group against challenge with WSSV. This result suggests that boosting with the antigen protein elicit stronger immune responses similar to adaptive immune responses of vertebrates. However, the short $TD_{50}$ was observed in the group challenged at 3 weeks post boosting comparing to the group challenged at 1 week post boosting. This suggests that the protective strength of immunization decreased by the time.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3989-3995
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• 2012

The aim of the present investigation was to evaluate the effect of A.nilotica extract against Dalton's ascitic lymphoma (DAL) induced solid and ascitic tumors in BALB/c mice. Experimental animals received A.nilotica extract (10 mg/kg.bw) intraperitoneally for 10 and 14 consecutive days before induction of solid and ascitic tumors, respectively. Treatment with A.nilotica extract significantly decreased the development of tumor and percentage increase in body weight when compared to DAL induced solid tumor control group, also increasing the life span, restoring the total white blood cell count and hemoglobin content and significantly decreasing the levels of serum aspartate transaminase (SGPT), alanine transaminase (SGOT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and nitric oxide (NO) when compared to DAL induced ascitic tumor controls. The treatment also reduced significantly the cellular glutathione (GSH) and nitric oxide levels in treated animals. Histopathological studies also confirmed protective influence. The outcome of the present work indicates that A.nilotica extract could be used as natural anticancer agent for human health.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1515-1518
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• 2012

Aim: We conducted a prospective study in an Chinese population to detect the association between GSTM, GSTT and GSTP gene polymorphisms and survival of gastric cancer. Methods: A prospective follow-up study with 317 gastric cancer patients was conducted between January 2003 and January 2005. GSTM1, GSTT1 and GSTP1 genotyping was performed using ABI TaqMan Gene Expression assays. Results: Of 317 patients, 5 were lost to follow-up due to migration, while the remaining 302 patients completed the study. The median follow-up time was 34.2 months (range: 2 to 60 months), during which a total of 120 (39.1%) died of gastric cancer. The GSTT1-null genotype showed a significant increased risk of death from gastric cancer, with an HR (95% CI) of 1.59 (1.04-3.58). Moreover, we found individuals carrying null-GSTM1 and null-GSTT1 had a moderate higher risk of death from gastric cancer, with an HR of 1.92 (1.05-3.65). Conclusion: This study reported the carriage of null GSTT1 and null GSTM1 might be linked to the higher death risk from gastric cancer in Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6263-6267
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• 2012

Background: Glutathione-S-transferase (GST) is an important phase II xenobiotic compound metabolizing enzyme family, involved in tolerance to a particular drug or susceptibility to a diseasec. This study focused the GSTM1 and T1 null allele frequency in the Gujarat population with a comparison across other Inter- and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Methods: DNA was isolated by a salting out method and GSTM1 and T1 homozygous null genotypes were detected by multiplex polymerase chain reaction in 504 unrelated individuals. The genotype distribution of null alleles was compared with Indian and non Indian ethnics reported earlier in the literature using Fisher's test. Results: The frequencies of the homozygous null genotypes of GSTM1 and GSTT1 were 20% (95%CI 16.7-23.9) and 35.5% (95%CI 31.4-39.9) respectively. GSTM1 null frequency did not deviate from most other Indian ethnic groups but differed from the majority of those of non Indian ethnicity studied. The frequency of homozygous null type of GSTT1 was significantly higher and deviated from all Indian groups and a few of non Indian ethnicity. Conclusions: Gujarat ethnicity, possibly the most susceptible for GSTT1 dependent drug disposition and diseases regarding effects of pollution. Further, the results have implications for GSTT1 dependent drugs used for treatment, a serious problem which needs to be solved by physicians and clinical researchers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4049-4052
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• 2013

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4235-4238
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• 2013

Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 ${\mu}M$) for 24 hours. Glucoraphanin at higher concentration (25 ${\mu}M$) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 ${\mu}M$. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen-metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2325-2331
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• 2011

Human CDX1 and CDX2 genes play important roles in the regulation of cell proliferation and differentiation in the intestine. Hox genes clustered on four chromosomal regions (A-D) specify positional signaling along the anterior-posterior body axis, including intestinal development. Using glutathione S-transferase (GST) pulldown assays, molecular interaction measurements, and fluorescence measurements, we found that the homeodomains (HDs) of CDX1 and CDX2 directly interact with that of HOXD8 in vitro. CDX1 showed significant affinity for HOXD8, but CDX2 showed weak affinity for HOXD8. Thus far, three-dimensional structures of CDX1/2 and HOXD8 have not been determined. In this study, we developed a molecular docking model by homology modeling based on the structures of other HD members. Proteins with mutations in the HD of CDX1 (S185A, N190A, T194A, and V212A) also bound to the HD of HOXD8. Our study suggests that the HDs of CDX1/2 resemble those of HOXD8, and we provide the first insight into the interaction between the HDs of CDX1/2 proteins and those of HOXD8.