The structurally diverse peroxisome prolifer- ators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate ((EtHx)2>Pht) increase the activities of hepatic catalase and peroxisomal fatty acid f8-oxidation enzymes in conjunction with... more
The structurally diverse peroxisome prolifer- ators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate ((EtHx)2>Pht) increase the activities of hepatic catalase and peroxisomal fatty acid f8-oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to delineate the level at which these enzymes are induced in the liver, the transcriptional activity of specific genes for fatty acyl-CoA oxidase (FAOxase) and enoyl-CoA hydratase/3- hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE), the first two enzymes of the peroxisomal fl-oxidation system, and for catalase were measured in isolated hepatocyte nuclei obtained from male rats following a single intragastric dose of ciprofibrate, clofibrate, or (EtHx)2>Pht. All three peroxisome proliferators rapidly increased the rate of FAOxase and PBE gene transcription in liver, with near maximal rates (9-15 times control) reached by 1 hr and persisting until at least 16 hr after administra...
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Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation,... more
Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), sphingosine kinase 1, and sphingosine kinase 2. Engagement of IgE to the FcεRI receptor induces the activation of both the SphKs and generates S1P. Furthermore, SphKs are also essential to FcεRI-mediated MC activation. Activated MCs export S1P into the extracellular space and causes inflammatory response and tissue remodeling. S1P signaling has dual role in allergic responses. Activation of SphKs and secretion of S1P are required for MC activation; however, S1P signaling plays a vital role in the recovery from anaphylaxis. Several non-coding R...
We have determined the gene expression of sphingosine-1-phosphate (S1P) metabolizing enzymes (SphK1, SphK2, SGPL1, SGPP1, SGPP2, PPAP2A, PPAP2B, and PPAP2C) by quantitative real-time polymerase chain reaction in tumor tissues and adjacent... more
We have determined the gene expression of sphingosine-1-phosphate (S1P) metabolizing enzymes (SphK1, SphK2, SGPL1, SGPP1, SGPP2, PPAP2A, PPAP2B, and PPAP2C) by quantitative real-time polymerase chain reaction in tumor tissues and adjacent normal tissues of 50 oral squamous cell carcinoma (OSCC) patients. Expression of SphK1 and SGPP1 genes was up-regulated significantly in 70% and 75% OSCC tumors respectively. Importantly, expression of SphK2 and PPAP2B was down-regulated in the tumor tissues of 70% OSCC patients. Expression of SphK2 and PPAP2B negatively correlated with tumor-node-metastasis (TNM) staging and tumor volume respectively. Furthermore, LPP1 is an independent predictor of TNM staging and lymph node ratio.
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Swiss albino mice were exposed to formulated cypermethrin (CMR) and/or or chlorpyrifos (CPF) through oral gavages for 60 days. Test doses of CMR (0.69, 1.38 or 2.76mg/kg/day) or CPF (0.5, 1.0 or 2.0mg/kg/day) or CMR + CPF (0.69 + 0.5,... more
Swiss albino mice were exposed to formulated cypermethrin (CMR) and/or or chlorpyrifos (CPF) through oral gavages for 60 days. Test doses of CMR (0.69, 1.38 or 2.76mg/kg/day) or CPF (0.5, 1.0 or 2.0mg/kg/day) or CMR + CPF (0.69 + 0.5, 1.38 + 1.0 or 2.76 + 2.0mg/kg/day) were based on the acute oral median lethal doses of CMR or CPF. Chromosome aberrations (CA), micronucleus (MN) induction, cell cycle perturbations, apoptosis and reactive oxygen species (ROS) generation were analysed in bone marrow cells. To explore the involvement of ROS induction, HaCat cells were exposed in vitro to arbitrary concentrations of CMR and/or CPF. Exposure of CMR (2.76mg/kg/day) induced significant inhibition of mitotic index. Significant (P < 0.01) frequencies of CA and MN were observed with the CMR at 1.38mg/kg/day, whereas CPF or its mixture CMR + CPF showed at highest doses. Chromosome/chromatid breaks and fragments were found to be major aberrations in all the treatment groups. Highest doses of ...
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Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns... more
Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. The sample frame was the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Offspring of Individuals with Diabetes Study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 μU/mL (Group E, ≥74 μU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;73.0 μU/mL and 120-min insulin &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;80.0 μU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin ≥73.0 μU/mL or 120-min insulin ≥80.0 μU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance.
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ABSTRACT The possibility of a co-exposure of furfural and kerosene and the ability to exhibit the toxic effects of such a mixture were examined in view of the toxicity potential of the two alone and in combination with each other.
Cytokines mediate the pathophysiology of the systemic inflammatory response syndrome (SIRS) associated with sepsis. Understanding of the precise role of individual mediator systems is extremely limited. In particular, IL-1 and IL-10 has... more
Cytokines mediate the pathophysiology of the systemic inflammatory response syndrome (SIRS) associated with sepsis. Understanding of the precise role of individual mediator systems is extremely limited. In particular, IL-1 and IL-10 has uncommonly been studied. The aim of the present study was to determine the pre and postoperative serum level of interleukin 1 and interleukin 10 cytokine in patients undergoing major surgery and to correlate these cytokines with postoperative sepsis development. 239 patients undergoing major elective surgery were recruited in study. Blood was sampled pre and postoperatively for the determination of cytokine IL-1 and IL-10. All patients were followed for 1 month following surgery for any evidence of sepsis. Serum cytokine IL-1 and IL-10 levels were measured through ELISA. Cytokine levels were related to the occurrence of sepsis if any. 19.66%(n=47) patients developed sepsis following surgery. Significantly higher levels of cytokine IL-10 (p< 0....
We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in... more
We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in groundwater. Blood samples were collected for DNA isolation to conduct polymorphic determination of genes, namely:NQO1(C609T),hOGG1(C1245G),GSTT1,andGSTM1(deletion). Symptomatic exposed subjects(n=38)were compared with asymptomatic exposed subjects(n=108)along with asymptomatic controls(n=148)from a non contaminated reference community. Exposed symptomatic group consisted of 36.8% subjects who wereGSTM1null genotyped as compared to asymptomatic where only 19.4% subjects were null. The exposed subjects withGSTM1null genotype were more susceptible to dermal adversities in comparison with wild genotyped subjects (OR = 2.42; 95% CI = 1.071–5.451). Age, smoking, gender or duration of residence were not found to have any confounding effect towards this association. ...
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Research Interests: Adolescent, Humans, Female, Male, Sepsis, and 15 moreRisk factors, Clinical Sciences, Middle Aged, Genotype, Adult, Odds ratio, Biological markers, Risk Factors, Genetic Markers, Enzyme Linked Immunosorbent Assay, Preoperative Period, Interleukin, Postoperative Period, Postoperative Complications, and Gastrointestinal surgery
[3H][2-methyl-2-p-(1,2,3,4-tetrahydro-naphthyl)phenoxy] propionic acid (nafenopin), a hepatocarcinogenic peroxisome proliferator, when administered p.o. to normal intact and partially hepatectomized male F344 rats did not show any... more
[3H][2-methyl-2-p-(1,2,3,4-tetrahydro-naphthyl)phenoxy] propionic acid (nafenopin), a hepatocarcinogenic peroxisome proliferator, when administered p.o. to normal intact and partially hepatectomized male F344 rats did not show any significant binding to DNA and RNA, but bound to proteins. The in vitro incubation of [3H]nafenopin and [3H]4-chloro-[6-(2,3-xylidino)pyrimidinylthio]acetic acid (Wy-14643), another peroxisome proliferator, with hepatic microsomes and calf thymus DNA also showed no significant binding of these chemicals to DNA.
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Hepatotoxic effects of n-hexane and n-heptane administered i.p. (1 ml/kg body wt) were studied in albino rats after 1, 2, 7 and 45 days of treatment. Hepatic protein content decreased with n-heptane and total sulphydryl content showed a... more
Hepatotoxic effects of n-hexane and n-heptane administered i.p. (1 ml/kg body wt) were studied in albino rats after 1, 2, 7 and 45 days of treatment. Hepatic protein content decreased with n-heptane and total sulphydryl content showed a significant decrease in the rats exposed to either solvent. A significant increase in lipid peroxidation was observed after 24 h and 48 h exposure to n-hexane or n-heptane. A marked decrease in drug metabolizing activity and an increase in pentabarbitone sleeping time was also observed. Hepatic glucose-6-phosphatase, a microsomal marker enzyme, showed a significant decrease.
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The genotoxic effects of oxidative metabolites of trichloroethylene (TCE), namely chloral hydrate, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCEOH) were examined in human peripheral blood lymphocytes. In... more
The genotoxic effects of oxidative metabolites of trichloroethylene (TCE), namely chloral hydrate, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCEOH) were examined in human peripheral blood lymphocytes. In this context, lymphocytes were exposed in vitro to 25, 50, and 100 μg/ml concentrations of these metabolites separately for a period of 48 h and examined for micronucleus (MN) induction through flow cytometer. At 50 μg/ml TCE metabolites, TCA (6.33 ± 0.56 %), DCA (5.06 ± 0.55), and TCEOH (4.70 ± 1.73) induced highly significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) frequency of MN in comparison to control (1.03 ± 0.40) suggestive of their genotoxic potential. However, exposure of 100 μg/ml of all the metabolites consistently declined the frequencies of MN which in some cases was equable to that of observed at 25 μg/ml. Further, cytotoxicity and cell cycle disturbances were also measured to find out the association of these endpoints with the MN induction. DNA content analysis revealed 3-4-fold elevation of S-phase at all the concentrations tested. Particularly, at 100 μg/ml, treatment elevation of S-phase was significantly (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) higher as compared to the control. Present findings together with earlier reports indicate that TCE induces genotoxicity through its metabolites. Interaction of these metabolites with DNA, as evident by elevated S-phase, seems to be the major cause of MN induction. However, involvement of spindle disruption cannot be ruled out. This comparative study also suggests that after TCE exposure, the metabolic efficiency of human to generate oxidative metabolites determines the extent of genotoxicity.
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ABSTRACT Real Time PCR is a sensitive technique with multidisciplinary applications such as detectionand quantification of genetically modified organisms(GMO’s), pathogens (bacteria, viruses), highthrough put screening of Single... more
ABSTRACT Real Time PCR is a sensitive technique with multidisciplinary applications such as detectionand quantification of genetically modified organisms(GMO’s), pathogens (bacteria, viruses), highthrough put screening of Single Nucleotide Polymorphism (SNP) within a population and expressionstudies. SYBR Green I an intercalating dye, used to discriminate genotypes/strains by meltingcurve analysis. Present paper discusses the discrepancy in melting temperature (Tm) for thesimilar PCR product using SYBR Green dye master mixes procured from different suppliers.Genes used in this study are ?-globin, Lectin, SPD a surfactant protein, Salmonella hinH2, Nosterminator and Virus (35S promoter). The article highlights the variation in melting temperaturethat may not be overlooked while performing SYBR green analysis. (On the basis of our results,one can conclude that proper recording of different kits used in specific experiments, isimportant for replicating the experiment in different laboratory setting. Tm parameter seemsto be a good tool to discriminate between PCR products of various GMO’s/strains provided onemake sure to use same kit.
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The present study assessed the frequency of intron 22 inversion mutation (Inv 22) in north Indian population with a cost analysis of different methods used for Inv 22 detection. We assessed the frequency of intron 22 inversion mutation in... more
The present study assessed the frequency of intron 22 inversion mutation (Inv 22) in north Indian population with a cost analysis of different methods used for Inv 22 detection. We assessed the frequency of intron 22 inversion mutation in a series of 181 cases with hemophilia A and also compared methods used for detection of the mutation including the long-distance PCR, Southern blot analysis, and inverse PCR in terms of cost, infrastructure, and technical input as well as turnaround time. The study group comprised 102 severe cases and 79 moderate cases of hemophilia A from a north Indian population of which 77 cases tested positive for Inv 22. The observed frequency of Inv22 mutation was 42.5%. Inv 22 resulted in a more severe phenotype and lower FVIII bioassay levels as compared to Inv 22 negative cases. Inv 22 positive cases also frequently presented with bleeding episodes at birth and the mean age for commencement of bleeding was lower (19 months) as compared to Inv-negative cases (50 months). The mean frequency of Inv 22 in cases with hemophilia A in a worldwide review is 44.25% of hemophilia A. Inv 22 can be conveniently detected by using the inverse PCR method. This technique is easy to standardize and lowest in cost.
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Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity still not much is... more
Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity still not much is known about its genotoxic potential on humans in relation to genetic polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs) are important in cellular detoxification of TCE. Variations in gene sequences result in population specific regional genetic variations (polymorphism). Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220 normal and 97 solvent-exposed individuals from northern part of India using real time PCR, PCR and restriction digestion techniques. The parameters examined to study genotoxicity were chromosomal aberration (CA) and cytokinesis block micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or (ile/val) or(val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9% respectively. It was further observed that the frequencies of above genes were found to be similar in solvent exposed groups. The distribution frequencies of GST genes, when compared with other reports from various regions of India show variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant genotoxic effect. TCE maybe toxic due to its metabolite.
Research Interests: India, Biological Sciences, Environmental Sciences, Humans, Environmental Biology, and 10 morePolymerase Chain Reaction, Genotype, Occupational Exposure, Genetic Polymorphism, Glutathione Transferase, Trichloroethylene, Lymphocytes, Restriction Mapping, Mutagenicity tests, and Medical and Health Sciences
Male F344 rats were fed a diet containing the peroxisome proliferators 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methyl- propionic acid (ciprofibrate (0.025%)) or (4-chloro-6-(2,3-xyli- dino)-2-pyrimidinylthio)acetic acid (Wy-14643 (0.1%))... more
Male F344 rats were fed a diet containing the peroxisome proliferators 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methyl- propionic acid (ciprofibrate (0.025%)) or (4-chloro-6-(2,3-xyli- dino)-2-pyrimidinylthio)acetic acid (Wy-14643 (0.1%)) for up to 14 months to determine whether hepatic peroxisome prolifera tion caused by these agents results in the induction of membrane lipid peroxidation in the liver. Peroxidative damage of membrane lipids from whole liver, postnuclear, heavy-particle, microsomal,
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The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2>Pht] increase the activities of hepatic catalase and peroxisomal fatty acid beta -oxidation enzymes in conjunction... more
The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2>Pht] increase the activities of hepatic catalase and peroxisomal fatty acid beta -oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to delineate the level at which these enzymes are induced in the liver, the transcriptional activity of specific genes for fatty acyl-CoA oxidase (FAOxase) and
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Glutathione S transferase (GST) gene polymorphism examined among north Indians and correlated with hydroquinone (HQ) genotoxicity to help in clinical prediction of susceptibility of HQ toxicity. Lymphocytes of individuals with/without... more
Glutathione S transferase (GST) gene polymorphism examined among north Indians and correlated with hydroquinone (HQ) genotoxicity to help in clinical prediction of susceptibility of HQ toxicity. Lymphocytes of individuals with/without GSTM1, GSTT1, and GSTP1 (ile/ile or val/val) were exposed to HQ (20, 40, or 80 microM) and examined chromosomal aberrations (CA) or cytokinesis-block micronucleus assays. Among north Indians the frequencies of GSTM1 (null), GSTT1 (null), and both null were found to be 41.1, 21.9, and 12.7%, whereas frequencies of GSTP1 with (ile/ile) or (ile/val), or (val/val) were 52, 42.1, or 5.9%, respectively. Individuals with null GSTM1, GSTT1, and GSTP1 (val/val) showed inhibition of mitotic index (MI) and significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) induction of CA as compared to individuals with GSTM1, GSTT1, and GSTP1 (ile/ile). Micronucleus formation was found to be significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 or 0.01) in both the genotypes. Results indicate that GSTM1, GSTT1 (null), and GSTP1 (val/val) are sensitive to HQ genotoxicity.
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Research Interests: Interaction, Transcription Factors, Gene expression, Molecular Mechanics, Estrogen Receptor, and 13 moreProtein-Protein Interaction, Female, Animals, Immunoprecipitation, Histone acetyltransferases, Rats, Rat, Utero, Uterus, Biochemistry and cell biology, Estrogen receptor-beta, Ovariectomy, and Estrogen receptor alpha
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Several hypolipidemic drugs and certain industrial plasticizers induce proliferation of peroxisomes, enhance the activity of peroxisome-associated beta-oxidation of fatty acids, and produce hepatocellular carcinomas in the livers of... more
Several hypolipidemic drugs and certain industrial plasticizers induce proliferation of peroxisomes, enhance the activity of peroxisome-associated beta-oxidation of fatty acids, and produce hepatocellular carcinomas in the livers of rodents. Because these chemicals themselves are not mutagens and do not covalently modify DNA, unlike the majority of chemical carcinogens, we proposed that the persistent proliferation of peroxisomes, and the induction of associated peroxisomal oxidases, caused a sustained increase in intracellular H2O2 or other reduced oxygen species, which would then introduce mutagenic DNA damage. In the present study, we investigated the ability of peroxisomes purified from the livers of normal and hypolipidemic drug-treated rats to induce DNA strand scission in vitro. Gradient-purified peroxisomes from livers of hypolipidemic drug-treated rats produced a 30- to 70-fold increase in H2O2 generation when compared to controls. The levels of H2O2 generated in incubations containing control or hypolipidemic drug-induced peroxisomes correlated well with the induction of single strand breaks in supercoiled simian virus 40 DNA molecules that were included in these reconstituted peroxisome incubations. Addition of excess catalase to peroxisome incubations failed to prevent strand breaks, suggesting that other reduced oxygen species may be rapidly generated from H2O2. These experimental results are consistent with a mechanism of hepatocarcinogenesis in which hepatocellular genetic damage is introduced by the by-products of peroxisomal fatty acid beta-oxidation, an oxidative pathway that is dramatically increased in hypolipidemic drug-treated livers.
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Lung cancer (LC) is the leading cause of cancer-related mortality in developing as well as developed countries. Life style choices, particularly tobacco smoking, have been implicated as the main cause in the development of the LC. Despite... more
Lung cancer (LC) is the leading cause of cancer-related mortality in developing as well as developed countries. Life style choices, particularly tobacco smoking, have been implicated as the main cause in the development of the LC. Despite the fact that majority cases of the LC occur among smokers, only 1-15% of smokers develop LC. In the present study, we have explored the role of genetic polymorphism, smoking habit and their association to LC in a cohort of north Indian population. The polymorphic genes explored were CYP1A1, GSTM1, GSTP1 and GSTT1 using techniques of Polymerase chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), Real Time PCR (RT PCR), and gene sequencing. Genetic polymorphism was analysed in 253 normal participants (control) and 93 LC patients originating from Lucknow, India. Data were compared using odds ratio and Fisher Exact Test. We found that smoking increases the susceptibility to LC threefold (OR = 2.9; 95% CI: 0.9-2.8). The most significant risk for LC (OR = 3.2; 95% CI: 0.7-3.8) was found in the association of the homozygous variant of CYP1A1 gene at A2455G base change at Exon 7 (Val/Val) genotype. There was a marginally significant association between LC and GSTT1 null genotype (OR = 1.3; 95% CI: 1.0-1.7) while no significant risk association was found between GSTP1 polymorphism and LC. The present study demonstrates that the presence of null genotype of GSTM1/GSTT1 taken together with CYP1A1 (Val/Val) genotype increases the susceptibility to LC eightfold in comparison to CYP1A1 (Ile/Ile) and GSTM1/ GSTT1 genotype.
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Research Interests: Environmental Toxicology, DNA damage, Biological Sciences, Insecticides, Environmental Sciences, and 17 moreHumans, Nitriles, Mice, Animals, Male, CHEMICAL SCIENCES, Micronucleus, Rats, Pyridines, Wistar Rats, Lymphocytes, Environmental, Mutagens, Mitotic Index, Cyclophosphamide, Thiazines, and Bone Marrow Cells
Hepatocarcinogenic peroxisome proliferators, clofibrate, ciprofibrate, Wy-14643 or di(2-ethylhexyl)phthalate, were administered once daily by gavage to groups of three male F344 rats for 3 days and the rats were killed 2 h after the last... more
Hepatocarcinogenic peroxisome proliferators, clofibrate, ciprofibrate, Wy-14643 or di(2-ethylhexyl)phthalate, were administered once daily by gavage to groups of three male F344 rats for 3 days and the rats were killed 2 h after the last dose. The DNA isolated from the livers was analyzed for possible carcinogen-DNA adducts, by a most sensitive 32P-postlabeling technique which can detect one adduct in 10(10) nucleotides. No adducts were detected by this assay in the DNA isolated from the livers of rats treated with any of the peroxisome proliferators. Adducts were also not found in the DNA of hepatocytes exposed in vitro to these peroxisome proliferators for 4 h in primary suspension cultures. Failure to detect peroxisome proliferator DNA adducts in hepatocytes under in vivo and in vitro conditions supports the contention that formation of a peroxisome proliferator-DNA adduct is not an essential step in the carcinogenesis by this novel class of carcinogens.
Research Interests: DNA, Liver, Animals, Male, Carcinogens, and 5 moreCarcinogenesis, Rats, Clofibric Acid, #Hypolipidemic Agents, and Clofibrate
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Promoter methylation and relative gene expression of O(6)-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell... more
Promoter methylation and relative gene expression of O(6)-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced tran...