• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.69-73
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• 2012

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ${\pm}$ S.D) $42.3{\pm}13.4$ years) and unrelated non-malignant controls (76 male and 48 females; age (mean ${\pm}$ S.D) $41.5{\pm}12.9$). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

• Molecular & Cellular Toxicology
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• v.2 no.1
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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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.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.688-693
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• 2007

The hepatoprotective effects of water extracts composed of Adenophora triphylla var japonica Hara (ATJH) on acetaminophen (APAP)-induced hepatotoxicity were investigated in vivo and in vivo. The effects of ATJH on liver toxicity induced by APAP were assessed by blood biochemical and histopathological analyses. APAP treatment (350 mg/kg) caused severe liver injury in mice as indicated by their significantly elevated plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pretreatment with ATJH for 3 or 7 days attenuated the increases in ALT and AST when challenged with APAP. The reductions in viability caused by high dose of APAP (450 mg/kg) in vivo were reversed by pretreatment with ATJH. These protective effects of ATJH against APAP-induced toxicity were consistent with the results from the histopathological examinations. We next examined the effects of ATJH on the gene expression of glutathione S-transferases (GSTs) that detoxify the metabolic intermediates of APAP in H4IIE cells. The hepatic GST protein levels [$\alpha$ class (GSTA2, GSTA3/5)] were significantly elevated in a dose-dependent manner by ATJH treatment. In summary, ATJH is effective at protecting against APAP-induced hepatotoxicity by GST induction, implying that ATJH should be considered a potential chemopreventive agent.

• Journal of Sericultural and Entomological Science
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• v.53 no.2
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• pp.135-142
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• 2015

The American cockroaches, Periplaneta americana L. was the most important worldwide pest species. It has been an public health problems. We were determinated life cycle and extraction of crude extracts by chemical reagents from cockraches (P. americana L.). The extracted crude solution has been antibacterial activity to gram negative bacteria (Pseudomonas aeruginosa, $6.44{\pm}1.03mm$), gram positive bacteria (Bacillus subtilis, $1.88{\pm}0.40mm$), and fungus (Candida albicans, $5.61{\pm}0.57mm$) using radial diffusion assay. We were analysed of up-regulation of Glutathione-S-transferases (GSTs) stimulation, indicating that antioxidantial protein from various classes are simultaneously expressed in a single insect upon infection or injury. The gene from Periplaneta americana L. were cloned, analysed sequence, and measured protein expression by Real Time PCR (Polymerase Chain Reaction).

• Korean journal of applied entomology
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• v.61 no.1
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• pp.155-163
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• 2022

The application of fungicides is indispensable to global food security, and their use has increased in recent times. Fungicides, directly or indirectly, have impacted insects, leading to genetic and molecular-level changes. Various detoxification mechanisms allow insects to eliminate reactive oxygen species (ROS) toxicity induced by agrochemicals including fungicides. In the present study, we analyzed the mRNA expression levels of detoxifying enzymes in Tenebrio molitor larvae following exposure to non-lethal doses (0.2, 2, and 20 ㎍/µL) of a fungicide captan. Transcripts of peroxidases (POXs), catalases (CATs), superoxide dismutases (SODs), and glutathione-s-transferases (GSTs) were screened from the T. molitor transcriptome database. RT-qPCR analysis showed that TmPOX5 mRNA increased significantly 24 h post-captan exposure. A similar increase was noticed for TmSOD4 mRNA 3 h post-captan exposure. Moreover, the expression of TmCAT2 mRNA increased significantly 24 h post-treatment with 2 ㎍/µL captan. TmGST1 and TmGST3 mRNA expression also increased noticeably after captan exposure. Taken together, these results suggest that TmPOX5 and TmSOD4 mRNA can be used as biomarkers or xenobiotics sensors for captan exposure in T. molitor, while other detoxifying enzymes showed differential expression.