Precancerous and Non-Cancer Disease Endpoints of Chronic Arsenic Exposure: The Level of Chromosomal Damage and XRCC3 T241M Polymorphism

Kundu, Manjari and Ghosh, Pritha and Mitra, Sahita and Das, J K and Sau, T J and Banerjee, Saptarshi and States, J. Christopher and Giri, Ashok K (2011) Precancerous and Non-Cancer Disease Endpoints of Chronic Arsenic Exposure: The Level of Chromosomal Damage and XRCC3 T241M Polymorphism. Mutation Research, 706. pp. 7-12.

[img]

PDF
Restricted to IICB Scientists only

Download (293Kb) | Request a copy

    Abstract

    Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed de.cient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenicinduced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenicinduced skin lesions having similar arsenic exposure. XRCC3T241Mpolymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR = 0.45, 95% CI: 0.30–0.67], peripheral neuropathy [OR = 0.49; 95%CI: 0.30–0.82] and conjunctivitis [OR = 0.60; 95%CI: 0.40–0.92]. A signi.cant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/1204
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Mr Shyamal Nath
    Date Deposited: 02 Jan 2012 12:01
    Last Modified: 02 Jan 2012 12:01
    Official URL: http://dx.doi.org/10.1016/j.mrfmmm.2010.10.004
    Links:

    Actions (login required)

    View Item