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Genetic predisposition for dermal problems in hexavalent chromium exposed population.

ABSTRACT: 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, and GSTM1 (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 were GSTM1 null genotyped as compared to asymptomatic where only 19.4% subjects were null. The exposed subjects with GSTM1 null 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. Association with other genes was not statistically significant, nonetheless, possible contribution by these genes cannot be ruled out. In conclusion, variation in the polymorphic status of GSTM1 gene may influence dermal outcomes among residents from Cr(VI) contaminated areas. Further studies are therefore, needed to examine these observations among different population groups.

SUBMITTER: Sharma P

PROVIDER: S-EPMC3412088 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic predisposition for dermal problems in hexavalent chromium exposed population.

Sharma Priti P Bihari Vipin V Agarwal Sudhir K SK Goel Sudhir K SK

Journal of nucleic acids 20120726

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, and GSTM1 (deletion). Symptomatic exposed subjects (n = 38) were compared with asymptomatic exposed subjects (n = 108) al ...[more]

PMID: 22919465

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Project description:Significant occupational and environmental exposures to hexavalent chromium, a metal with broad toxicity potential in humans, have been reported. In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to a toxic concentration of potassium dichromate was performed. Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. Hierarchical cluster analysis of the gene expression profile demonstrated a clear separation of the treated cells from the control group of cells. Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. Induction of apoptosis and generation of hydroxyl radicals indicative of oxidative stress in the dermal fibroblasts in response to their exposure to hexavalent chromium were independently confirmed by TUNEL assay and electron spin resonance (ESR) analysis, respectively. The potassium dichromate-induced cytotoxicity, differential gene expression, apoptosis, and oxidative stress were significantly blocked by the addition of ferrous sulfate, an agent known for its ability to reduce hexavalent chromium to the insoluble and therefore impermeable trivalent form, to the cell culture medium. Taken together, our data provide insights into the potential mechanisms underlying the dermal toxicity of hexavalent chromium and suggest a definite role for apoptosis and oxidative stress in Cr(VI)-induced cytotoxicity in human dermal fibroblasts. 16 samples were analyzed in this experiment. Exponentially growing human dermal fibroblasts (3x105 cells) were cultured in T25 cell culture flasks. When the cells were approximately 70% confluent, hexavalent potassium dichromate (5µM) was added to the medium with or without 40µM ferrous sulfate. Following 16 hours of culturing at 37oC, total RNA was isolated for gene expression studies. Details of the samples are: Control 4 Samples: Cr(0)-1, Cr(0)-2, Cr(0)-3, Cr(0)-4 Cr 5 µM 4 Samples: Cr(5)-5, Cr(5)-6, Cr(5)-7, Cr(5)-8 FeSO4 40 µM 4 Samples: Fe(40)-9, Fe(40)-10, Fe(40)-11, Fe(40)-12 Cr 5 µM + FeSO4 40 µM 4 Samples: Cr(5)+Fe(40)-13,Cr(5)+Fe(40)-14, Cr(5)+Fe(40)-15, Cr(5)+Fe(40)-16

Project description:ObjectiveThe International Agency for Research on Cancer classifies hexavalent chromium (Cr(VI)) as a human carcinogen. As reported, cancer mortality was higher in Cr(VI)-contaminated areas. Scientists have recommended studying its health impact on people living in contaminated areas. This study aims to evaluate the health risk for people living in Cr(VI)-contaminated areas.DesignWe conducted a cross-sectional study in rural areas of north-eastern China. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were used as oxidative stress parameters, and 8-hydroxy-2 deoxyguanosine (8-OHdG) as a DNA damage biomarker. We collected information on demographics, lifestyles and length of residence from all participants using a questionnaire. Biological specimens and environmental media samples were collected on the same day as the survey was done. We used t-test, χ2 test, Wilcoxon rank-sum test and multivariate linear regression analysis.ParticipantsThe study included 319 participants exposed to Cr(VI) and 307 unexposed participants, with 447 women and 179 men. These participants met the following criteria: (1) living in the areas for more than 10 years; (2) age older than 18 years; and (3) without occupational chromium exposure.ResultsOur study revealed that serum concentration of MDA (p<0.001), serum activities of CAT (p<0.001) and GSH-Px (p<0.001), as well as urine concentration of 8-OHdG (p=0.008) in the exposed group were significantly higher than those in the unexposed group. However, serum SOD activity was significantly lower in the exposed group, compared with that in the unexposed group (p<0.001). Cr(VI) exposure and smoking have an interaction effect on GSH-Px activity (p<0.05). Cr(VI) exposure and alcohol drinking also have an interaction effect on GSH-Px activity (p<0.05). Longer residence in the exposed areas increased the oxidative levels (p<0.05).ConclusionsThe findings of this study showed elevated oxidative stress and DNA damage in people exposed to Cr(VI).

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Genetic predisposition for dermal problems in hexavalent chromium exposed population.

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Genetic predisposition for dermal problems in hexavalent chromium exposed population.

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