6 research outputs found
Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India
Abstract Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.</p
Arsenic Exposure Through Drinking Water Increases the rRsk of Liver and Cardiovascular Diseases in the Population of West Bengal, India
Background: Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India.
Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The
aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver
enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and
anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population.
Methods: Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status
was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased
cardiovascular disease risk, IL6, IL8 and MCP-1 were determined.
Results: Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline
phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased
in the arsenic exposed group.
Conclusions: Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and
imparts increased cardiovascular risk.
Keywords: Arsenic, Antinuclear antibody, Liver function tests, Cytokine
Polymorphisms in the TNF-α and IL10 Gene Promoters and Risk of Arsenic-Induced Skin Lesions and Other Nondermatological Health Effects
In West Bengal, India, at present, more than 26 million people are exposed to arsenic through drinking water. Among them, only 15–20% manifest arsenic-induced noncancerous, precancerous, and cancerous skin lesions, indicating that genetic variants play important role in arsenic susceptibility. Chronic arsenic exposure has been associated with impairment of immune systems in the exposed individuals. Because cytokines are important immune mediators, alteration in expression of these gene products may lead to arsenic-specific disease manifestations. The aim of the present work was to investigate the association between the TNF-α−308G>A (rs1800629) and IL10 −3575T>A (rs1800890) polymorphisms and arsenic-induced dermatological and nondermatological health outcomes. A case-control study was conducted in West Bengal, India, involving 207 cases with arsenic-induced skin lesions and 190 controls without skin lesions having similar arsenic exposure. The polymorphisms were determined using conventional PCR-sequencing method. ELISA was done to determine the serum levels of the two cytokines tumor necrosis factor α (TNF-α) and interleukin 10 (IL10). Associations between the polymorphisms studied and nondermatological health effects in the study subjects were determined from our epidemiological survey data. Individuals with GA/AA (−308 TNF-α) and TA/AA (−3575 IL10) genotypes were at higher risk of developing arsenic-induced skin lesions, ocular, and respiratory diseases. Also the −308 TNF A allele corresponded to a higher production of TNF-α, and −3575 IL10 A allele corresponded to a lower production of IL10. Thus, the polymorphisms studied impart significant risk toward development of arsenic-induced dermatological and nondermatological health effects in the chronically exposed population of West Bengal, India
PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage
Poly(ADP-ribose) polymerases (PARP) attach poly(ADP-ribose) (PAR) chains to various proteins including themselves and chromatin. Topoisomerase I(Top1) regulates DNA supercoiling and is the targetof camptothecin and indenoisoquinoline anticancer drugs, as it forms Top1 cleavage complexes
(Top1cc) that are trapped by the drugs. Endogenous
and carcinogenic DNA lesions can also trap Top1cc.
Tyrosyl-DNA phosphodiesterase 1 (TDP1), a key
repair enzyme for trapped Top1cc, hydrolyzes the
phosphodiester bond between the DNA 30-end and
the Top1 tyrosyl moiety. Alternative repair pathways
for Top1cc involve endonuclease cleavage. However,
it is unknown what determines the choice between
TDP1 and the endonuclease repair pathways. Here
we show that PARP1 plays a critical role in this
process. By generating TDP1 and PARP1 doubleknockout
lymphoma chicken DT40 cells, we demonstrate
that TDP1 and PARP1 are epistatic for the
repair of Top1cc. The N-terminal domain of TDP1
directly binds the C-terminal domain of PARP1, and
TDP1 is PARylated by PARP1. PARylation stabilizes
TDP1 together with SUMOylation of TDP1. TDP1
PARylation enhances its recruitment to DNA
damage sites without interfering with TDP1 catalytic
activity. TDP1–PARP1 complexes, in turn recruit X-ray
repair cross-complementing protein 1 (XRCC1). This work identifies PARP1 as a key component driving
the repair of trapped Top1cc by TDP1
Chronic Arsenic Exposure Impairs Macrophage Functions in the Exposed Individuals
Introduction Owing to the established roles of human
macrophages in immune defense, we investigated the effect
of chronic arsenic exposure upon these major hematopoietic
cells in 70 arsenic-exposed individuals with skin lesions
and 64 unexposed individual