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ABSTRACT: To investigate the association of glutathione-S-transferase (GST) polymorphisms with the risk of acute myeloid leukemia (AML), a meta-analysis of case-control studies published between 1998 and 2009 was performed. Pooled odds ratios (ORs) were assessed using both fixed- and random-effects models. Heterogeneity across studies was calculated, and funnel plots were constructed to test for publication bias. Overall, the random-effects OR with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.30 (95% confidence intervals (CI) 1.04-1.62, p = 0.018), 1.03 (95% CI 0.80-1.33, p = 0.80) and 1.24 (95% CI 0.98-1.58, p = 0.06), respectively. Statistically, significant increased risk of AML was observed with GSTM1 while borderline significance was seen with GSTT1 null genotypes. However, fixed-effects model showed significant risk of AML in the presence of null genotypes of GSTM1 and GSTT1(p < 0.05). Significant heterogeneity was found between studies relating to GSTP1 (p = 0.162), however, no heterogeneity was seen in studies that evaluated GSTM1 (Q-value = 44; I(2) = 70.9; p-value < 0.01]; and GSTT1 (Q-value = 26.03; I(2) = 57.74; p-value < 0.01] polymorphisms. From the limited studies on the association of GSTP1 with risk of AML, the role of this gene cannot be ascertained fully. Significant association of these three genes with risk of AML must be evaluated further with respect to population, smoking, eating habits, ethnicity, and race.
Leukemia & lymphoma 08/2009; 50(8):1345-51. · 2.40 Impact Factor
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ABSTRACT: The present study was undertaken to investigate lead-induced toxicity in occupationally exposed humans and to evaluate whether genetic damage can be correlated with the known clinical indicators of lead poisoning. For this purpose, genotoxicity biomarkers along with some clinical indices of lead poisoning were determined in blood samples of battery plant workers and compared with healthy control subjects. Workers had significantly increased chromosomal aberrations, micronuclei and DNA damage compared to the controls. Increased blood lead levels (BLLs), decreased hemoglobin, PCV and symptoms of lead poisoning were used as clinical indices of lead toxicity. In addition gene polymorphisms in ALAD and MGP gene were investigated and correlated with BLL and hemoglobin content. Our results showed no significant effects of the ALAD G177C polymorphism on BLL concentrations and BLL concentrations varied to levels much above the normal reference ranges independent of the genotype. Although, significance could not be achieved, ALAD 1-2/2-2 type subjects had numerically higher BLLs (76.2-89.1 microg/dl), compared to ALAD 1-1 volunteers (21.8-79.1 microg/dl). Similarly, this study also aimed to identify the relation of some SNPs with emphasis on lead toxicity and since MGP gene is an important biomarker associated with calcium metabolism; it was hypothesized that it may be associated with lead toxicity. However, we did not find any significant association of MGP T-138C and lead poisoning. Further studies on the role of gene polymorphisms over a larger population along with genotoxicity parameters and biochemical analyses may serve to understand lead toxicity.
Journal of hazardous materials 04/2009; 168(2-3):918-24. · 4.14 Impact Factor
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ABSTRACT: Matrix gamma-carboxy glutamic acid protein (MGP) is a 10-kDa secreted protein containing five residues of the vitamin K-dependent calcium binding amino acid gamma-carboxyglutamic acid (Gla). This study was carried out to examine the effects of MGP gene promoter polymorphism (T-138C) on blood lead levels (BLL) and hematological parameters in 113 battery manufacturing unit workers occupationally exposed to lead and 102 controls. Genotypes for the MGP T-138C polymorphism were determined by PCR and restriction fragment length digestion. BLL were determined by Anode Stripping Voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture (CBP) was analyzed using ADVIA Cell counter for each sample. The frequencies of MGP-TT, CT and CC genotypes in our population were 38.6%, 44.3%, and 17.2%, respectively. The frequencies for T and C alleles were 0.612 and 0.386, respectively. Although BLL did not differ significantly among genotypes; they were higher in workers with TT/CT genotype compared to CC genotype subjects (76-88 microg/dL vs 22-45 microg/dL, p > 0.05). About 29.2% of volunteers (n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 gms/dl. There was no significant difference in total white cell count and platelet count between occupational and non-exposed groups. The possible role of SNPs in the promoter region of MGP gene with relation to lead toxicity was investigated for the first time in the Indian population; although significance could not be achieved in this study, further assessments over a larger population size may help in better understanding of the consequences of lead exposure.
Toxicology mechanisms and methods 03/2009; 19(3):209-13. · 1.03 Impact Factor
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ABSTRACT: Two common polymorphisms in cytochrome P450; family 1, subfamily A, polypeptide 1 (CYP1A1); have been implicated as a risk factor of prostate cancer, but individual studies have been inconclusive or controversial. We reviewed studies on CYP1A1 polymorphisms in patients with prostate cancer.
The strategy searching in the PubMed was based on combinations of prostate cancer, CYP1A1, CYP1A1 gene polymorphism, and genetic susceptibility. The last search update was May 2008. The retrieved articles and their bibliographies of were evaluated and reviewed independently by 2 experts. We shortlisted 19 studies, of which 14 on sporadic prostate cancer were analyzed. Overall, 2573 patients with prostate cancer and 2576 controls were analyzed.
The random effects odds ratio was 1.350 (95% confidence interval, 1.110 to 1.641; P = .003) for T/C polymorphism and 1.085 (95% confidence interval, 0.863 to 1.364; P = .49) for A/G polymorphism. The A/G polymorphism was not associated with increased risk of prostate cancer. However, the T/C polymorphism showed conflicting results in different studies, while overall, this polymorphism showed significant effects on the susceptibility to prostate cancer. There was no significant between-study heterogeneity for both polymorphisms with respect to distribution of alleles.
This meta-analysis suggests that while the CYP1A1 T/C polymorphism is likely to considerably increase the risk of sporadic prostate cancer on a wide population basis, the A/G polymorphism may not influence this risk. However, the association of polymorphisms may be significant with respect to smoking history, diet habits, ethnicity, and race.
Urology journal 02/2009; 6(2):78-86. · 0.58 Impact Factor
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ABSTRACT: Organophosphorus pesticides like monocrotophos, profenofos, chlorpyrifos, and acephate are most commonly used in India for agriculture and public health programs. Previous studies have revealed that at low doses, organophosphorus pesticides not only act as genotoxic agents but also affect several other biochemical pathways. The aim of the current investigation was to assess apoptosis and necrosis caused by these pesticides on human peripheral blood lymphocytes under in vitro conditions using the DNA diffusion assay. Our studies have revealed that all the above pesticides induced apoptosis and necrosis in cultured human peripheral blood lymphocytes in in vitro conditions. The results are statistically significant (p < 0.001). Data on these alterations of immune cells are required for understanding the subchronic effects mediated by pesticides on nontarget organisms.
Drug and Chemical Toxicology 02/2006; 29(2):147-56. · 1.08 Impact Factor
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ABSTRACT: Lead is a known toxicant that has been implicated in encephalopathy in children and may affect the gastrointestinal and hematopoietic and other systems in adults. In fact, lead has been shown to compete with calcium for entry into the synaptosome and induce toxic effects. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of lead by using lymphocytes from human peripheral blood in vitro. The LC50 for lead nitrate as determined by Trypan blue dye exclusion technique was found to be 3.14 mM. Chromosomal aberration frequency at sublethal doses (1/10 of LC50) as determined by examining the metaphase chromosomes (karyotyping) did not show significant aberrations except for some aneuploidy and about 2-4% gaps, breaks (3-4%), and about 5% satellite associations. However, significant DNA damage was determined by SCGE (Comet assay). The comet tail length proportionately increased with increasing lead nitrate concentration. Thus, Pb can induce single-strand DNA breaks, possibly by competing with metal binding sites.
Drug and Chemical Toxicology 02/2006; 29(1):111-24. · 1.08 Impact Factor
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ABSTRACT: Profenofos is a broad-spectrum organophosphate insecticide and acaricide used widely for agricultural and household purposes. The aim of this investigation was to determine its toxicity profile in vitro, using lymphocytes from peripheral blood samples of healthy human donors. We found the IC(50) of profenofos to be 3.5 microM as measured by Trypan blue dye exclusion method. Chromosomal analyses of the metaphase plates of the samples treated with sublethal concentrations of profenofos revealed satellite associations and chromatid breaks and gaps, indicating its effect on chromosomes. The results were further supported by comet assay, where single-strand breaks in DNA were observed as comet tail lengths. The results were statistically significant (p < 0.01, ANOVA). Hence, it may be proposed that in vitro assays like the comet assay and chromosomal aberrations test, which indicate genetic damage, could be used to study the effect of organophosphorus pesticide poisoning in humans.
Drug and Chemical Toxicology 01/2006; 29(3):313-22. · 1.08 Impact Factor
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ABSTRACT: The toxicological profile of the four pesticides described herein characterizes its effects on lymphocytes from peripheral blood from healthy donors. The exposure to all pesticides was by direct interaction/incubation with varying concentrations of the pesticide with blood sample in-vitro. The dose response relationship in each case was calculated by applying log tables as LC50 values. Cytotoxicity of these pesticides on lymphocytes was measured using the trypan blue dye exclusion technique. Based on LC50 value, all the four pesticides were found to be highly toxic to lymphocyte culture, among them, monocrotophos and endosulfan were the most toxic and dimethoate was the least toxic. The genotoxicity of the pesticides was also determined by comet assay. The results revealed that the pesticides caused increase in the tail length indicating DNA damage. This study suggests that these pesticides have the capacity to alter the genetic material particularly chromosomes in mammalian cultures. The comet assay used in this study was found to be a sensitive and rapid method to detect genotoxicity of pesticide compounds.
Drug and Chemical Toxicology 06/2004; 27(2):133-44. · 1.08 Impact Factor
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ABSTRACT: Epidemiological studies were conducted in pesticide-exposed agricultural workers along with an equal number of age-and sex-matched controls. All the 200 exposed volunteers were suffering from fever, nausea, headache and other abnormal symptoms and visited the hospital for general health check-up. These cases were taken up for more detailed studies. Five (2.5%) showed decrease in RBC, haemoglobin, and increase in WBC with a large number of immature cells. These volunteers were further diagnosed as Philadelphia-negative Chronic Myeloid Leukaemia (CML) cases based on clinical and pathological examinations. In similar environs, about 100 children (aged bet-ween 1 and 17 years) were studied for the above para-meters. About 3% of the exposed children showed signs of mental retardation and delayed milestones; these were compared with healthy children (age-and sex-matched) from pristine environment. It is therefore concluded that clinical evaluations supported by occu-pational epidemiology could determine CML in exposed individuals (adults). USAGE of pesticides in the ecosystem leads to develop-ment of various types of morphological, physiological, biochemical and behavioural changes in individuals 1,2 . The degree of toxicity depends upon the nature of the pesticides, their environmental concentration and factors such as temperature, humidity, pH, oxygen concentration, etc. Pesticides are chemicals designed to kill a variety of pests, such as weeds, insects, rodents and fungi. They can be characterized on the basis of their function as insecti-cidal, herbicidal, rodenticidal, fungicidal, etc. and also on the basis of chemical nature, i.e. organophosphates, orga-nochlorines, S-triazines and pyrethroids. Potentially haz-ardous environmental toxicants like pesticides display a broad spectrum of biological effects, being toxic not only to target organisms but also to humans. In a broad sense, every disease is caused either by environmental factors or genetic factors; the latter includes natural deterioration of the body with age. The objective of pesticide usage to prevent crop loss from insects remains unachieved. Widespread use of syn-thetic chemicals after the Second World War has revolu-tionized agricultural practice. Initial studies of the possible health effects of these substances on humans were small and reassuring. During the 1960s, however, it became evident that persistent usage of pesticides had an adverse impact on the ecological communities 3 . This led to a number of extensive epidemiologic investigations exploring the possible impact of these exposures on hu-man health. These studies faced numerous methodological problems common to environmental epidemiology, and even today, our understanding of the relationship between pesticides and human health is limited 4 . Improper usage of pesticides and usage of banned pesti-cides lead to neurological and haematological complications in individuals 5,6 . This is at a high incidence, especially in India where there is continuous usage of different pesti-cides, including banned ones, based on the season and crop produced. Household use of pesticides without prior knowledge of their toxic effects and use without safety precautions also lead to such incidents. Genotoxicity of pesticides on peripheral blood lymphocytes has been re-ported 7,8 . Cytotoxicity of pesticides has also been repor-ted 9–12 . Current understanding of carcinogenesis favours the conclusion that even a tiny dose of a genotoxic agent can initiate the process of converting a normal cell to a malignant one. The aim of this study was to examine the health outcomes of a group of agricultural workers occu-pationally exposed to pesticides in Andhra Pradesh, India. Most of the exposed groups were apparently healthy when they came to the hospital with minor ailments. Therefore occupational epidemiology consists of recording the data of such groups. Blood samples from 200 healthy adults, non-smoking, non-alcohol, i.e. with little or no exposure to pesticides were collected as controls. An equal number of blood samples was collected from male and female individuals (adults) exposed directly or indirectly to farm or indoor pesticide sprays and who came to the hospital with com-plaints and disease-like symptoms. Similarly, blood samples from 100 children living in clean environs along with an equal number of samples from children living in pesticide-prevalent environments were collected in sterile vacutainers containing anti-coagulant for epidemiological studies. This study was carried out with the approval of the Ethical Committee of Mahavir Hospi-tal and Research Centre and prior consent of the subjects (Annexures I and II). Blood samples obtained from the cases and controls were diagnosed for certain parameters. Epidemiological parameters were recorded according to the WHO norms where age, sex, exposure period and clinical symptoms and other associated parameters were systematically recorded as given below.
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