• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6429-6438
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• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• 한국식품과학회지
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• 제39권6호
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• pp.688-693
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• 2007

아세트아미노펜(APAP)으로 유도된 간독성 모델에 미치는 잔대를 주재료로 하는 추출물(ATJH)의 간보호 효능을 관찰하기 위하여 동물모델에서 혈청 간기능 지표효소의 활성도를 측정하고 조직학적인 변화를 관찰하였다. APAP를 투여한 동물군은 ALT와 AST활성을 현저하게 증가시켰다. ATJH를 1000 mg/kg의 용량으로 3일간 전투여한 후 APAP로 간 독성을 유도한 동물은 증가된 AST, ALT활성을 약 60-80% 감소시켰으며, 500 mg/kg의 용량으로 장기간(7일간) 전투여한 동물에서도 APAP독성방어효과가 현저하였다. APAP를 고농도(450 mg/kg)로 투여하여 간손상에 의한 사망을 유도한 동물군에서 ATJH는 생존율을 대조군에 비하여 130% 증가시켰다. APAP 단독 투여한 군에서 80-90% 정도 간세포 괴사가 관찰되었으나 ATJH(500, 1000 mg/kg)를 3일간 전투여 한 군에서는 간조직 손상이 억제되었다. 동물모델에서 ATJH에 의한 간독성 방어효능의 기전을 연구하기 위하여 간세포에서 제2상 해독화 효소인 GST의 단백 발현 변화를 면역화학적으로 관찰하였다. ATJH는 농도의존적으로 GSTA2, GSTA3/5의 단백 발현을 유의성있게 유도하였다. 본 연구에서는 잔대를 주원료로 한 추출물이 간세포의 해독화효소의 발현을 증가시킴으로서 APAP에 의해 유발된 간손상을 억제함을 처음으로 증명하였고, 간조직 보호를 위한 화학적 예방 효능을 갖는 활성물질로서 ATJH의 가능성을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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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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• 제13권9호
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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.

• The Plant Pathology Journal
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• 제24권4호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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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.

• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.275-284
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• 1998

1996년 3월부터 1996년 12월까지 충북대학교병원 비뇨기과에 입원하여 치료를 받은 방광암 환자 67명과 암 아닌 다른 질환을 가진 대조군 67명을 대상으로 흡연, 음주, 직업력 등을 포함한 생활 습관과 NAT2와 GSTM1, 그리고 GSTT1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. NAT2 다형성 분포는, 환자군이 slow, intermediate, rapid acetylator가 각각 3.0%, 38.8%, 58.2%, 그리고 대조군이 7.6%, 40.9%, 51.5%였으며, NAT2의 활성과 방광암 위험도 사이의 관련성은 유의하지 않았다($\chi^2_{trend}=1.18$, P-value>0.05). 2. GSTM1 결손은 환자군의 68.7%, 대조군의 49.3%에서 확인되었으며, OR(95% 신뢰구간)이 2.23(1.12-4.56)으로, 방광암 발생의 위험인자로 나타났다. 3. GSTT1은 환자군의 26.9%,그리고 대조군의 43.3%에서 결손이 있는 것으로 나타나서, GSTT1 결손은 방광암에 대하여 보호효과가 있는 것으로 관찰되었다(OR: 0.48, 95% 신뢰구간: 0.23-0.99). 4. 흡연 여부는 방광암의 발생에 유의한 영향을 미치지 않는 것으로 나타났는데(OR=1.85, 95% CI: 0.85-4.03), 이는 환자군과 대조군의 흡연률이 모두 높기 때문으로 판단된다. 5. 그 외, 음주력, 직업력, 수혈 여부, 그리고 피임시술의 과거력 등의 요인들은 방광암 발생과 유의한 관련성이 없는 것으로 나타났다.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.29-34
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• 2006

Immunoglobulin E (IgE) plays an important role in the development of allergic disorders including asthma. Cigarette smoking was reported to elevate serum IgE level and air pollutants such as $NO_{2}$ have been reported to modulate the immune system including inflammation. Moreover, genetic polymorphisms of glutathione S-transferases (GSTs) were reported to affect inflammatory diseases including asthma. Therefore, in the present study we tried to investigate whether tobacco smoke or $NO_{2}$ exposure increases the level of IgE and the GST gene polymorphisms are associated with change of IgE level due to tobacco smoke or $NO_{2}$ exposure. We measured urinary cotinine, personal $NO_{2}$ exposure, and serum IgE levels in 300 healthy university students without allergic disorders. Allelic loss of the GSTM1 and GSTT1 and the GSTP1 (lle105Val) polymorphism were determined by PCR and RFLP. Total serum IgE levels were significantly different according to urinary cotinine levels (P=0.046), while $NO_{2}$ passive dosimeter level and genetic polymorphisms of three GSTs were not associated with total IgE level. Moreover, subjects with cotinine $500\;{\mu}g/g$ creatinine or more showed the highest level of total IgE when they had null type of GSTM1, null type of GSTT1, or variant type of GSTP1 (P<0.05). When we considered IgE level according to urinary cotinine levels in strata with the combinations of GSTM1, GSTT1, and GSTP1 genetic polymorphisms, the subjects with GSTM1 null, GSTT1 null, and GSTP1 variant types showed the largest difference between IgE levels of subpopulations according to cotinine levels (P=0.030). However, there was no significant difference between IgE levels of subpopulations according to $NO_{2}$ passive dosimeter levels in any group with combinations of GSTM1, GSTT1, and GSTP1 polymorphisms. This result suggests that smoking increases allergic response measured as IgE level and combinations of the GSTM1, GSTT1, and GSTP1 polymorph isms modify the effect of smoking on serum IgE level.

• 한국잠사곤충학회지
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• 제53권2호
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• pp.135-142
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• 2015

본 연구는 미국바퀴(Periplaneta americana)의 식의약용 소재로의 활용을 위하여 미국바퀴의 사육 특성을 조사하여 사육의 편의를 제공하고, 유용물질의 분리 및 분석을 통하여 식의약용 소재로의 가능성을 제시하고자 하였으며, 그 결과로 미국바퀴는 한 개의 난포가 평균 25개의 알을 포란하고 있고, 14.5개의 알이 부화하여 약 67%의 부화율을 보였으며, $28^{\circ}C$에서 사육하는 것이 가장 효율적인 사육온도로 확인하였다. 미국바퀴(P. americana) 성충의 일반성분 및 유용성분 분석 결과, 일반성분 중 수분이 60% 이상을 차지하고 있으며, 조지방이 1%, 조단백질은 33.49 %로써 조단백질 함량이 높게 측정되었다. 필수아미노산이 2.37%를 차지하고 있으며, 지방산은 항암작용을 가지고 있는 oleic acid (C18 : 1n9c)가 28.91%, palmitic acid(C16 : 0)가 19.06%로 가장 많은 량을 차지하고 있어 미국바퀴의 식용화 가능성을 확인하였다. 미국바퀴(P. americana)는 성충을 멸균증류수(DW) 및 각종 유기용매(ethyl acetate, hexan, ethyl ether, EtOH, MeOH))로 추출하여 각각의 조추출물이 가지고 있는 항균 활성을 측정하기 위하여 그램 음성균인 P. aeruginosa, E. coli와 그램 양성균인 B. subtilis, S. auricularis와 진균인 C. abbicans을 대상으로 실시한 disc diffusion test의 결과, ethyl ether를 이용하여 추출한 조추출물이 시험에 사용된 각각의 공시균주에 대하여 B. subtilis $1.88{\pm}0.40mm$, S. auricularis $7.78{\pm}0.76mm$, P. aeruginosa $6.44{\pm}1.03mm$, E. coli $7.55{\pm}0.74mm$, C. abbicans $5.61{\pm}0.57mm$의 clear zone을 형성하면서 각각의 균주 생장을 저해하는 것을 확인하였으며, 온도 스트레스에 대한 항산화 물질인 GST 발현량을 Real Time PCR을 이용하여 정량분석 한 결과, 항산화 단백질인 GST는 $37^{\circ}C$에서 한 시간 단위로 점차 발현량이 증가하고, $4^{\circ}C$ 처리를 한 경우에는 1시간 경과 후 급격하게 증가하였으며, 2시간 경과한 후에 가장 많은 발현량을 보였다. 본 연구결과에 따라서, 미국바퀴(P. americana)는 각종 유용성분을 함유하고 있으며, 항균 활성도 우수한 것으로 확인하였고, 온도처리와 같은 사육조건 조절시 고품질의 원료생산을 통한 농가소득 증대에 기여할 수 있을 것으로 기대한다.

• 한국응용곤충학회지
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• 제61권1호
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• pp.155-163
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• 2022

최근 살진균제는 세계 식량 안보에 없어서는 안될 필수 요소이며, 그 사용량은 증가하고 있다. 살진균제는 직접적 또는 간접적으로 곤충에 영향을 미쳐 유전자 및 분자 수준의 변화를 일으킨다. 곤충은 다양한 해독 매커니즘을 통해 살진균제를 포함한 농약으로부터 유발되는 활성산소(ROS) 독성을 제거한다. 본 연구는 살진균제 캡탄의 비치명적 투여량(0.2, 2, and 20 ㎍/µL)을 주입 후 갈색거저리의 유충에서 해독효소의 mRNA 발현량을 분석했다. 갈색거저리의 전사체 분석을 통해 해독 매커니즘 관련 유전자인 퍼옥시다제(POX), 카탈라제(CAT), 슈퍼옥사이드 디스뮤타제(SOD) 및 글루타티온-S-트랜스퍼라제(GST)를 발굴하였다. 처리 24시간 후 TmPOX5 mRNA가 유의하게 증가한 것으로 나타났다. 처리 3 시간 후 TmSOD4의 mRNA가 유사하게 증가하였다. 또한 2 ㎍/µL 처리 24시간 후 TmCAT2의 mRNA 가 유의하게 증가하였다. 캡탄 노출 후 TmGST1 및 TmGST3의 mRNA 발현량도 증가하였다. 결론적으로, TmPOX5 및 TmSOD4 유전자는 갈색거저리에서 캡탄 노출에 대한 바이오마커 또는 생체이물 센서로 작용할 수 있음을 시사한다.