LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
LIFE09200604007 Tabish - Homi Bhabha National Institute
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Discussion<br />
death which is a safe way to inhibit risk acquiring neoplastic autonomy 107 . Therefore a<br />
failure in proper apoptotic response after extreme genotoxic exposure may also<br />
contribute to MPN development. There are reports available where disruption of<br />
apoptosis is associated with cancer 51, 53, 104, 105 . We observed that after radiation as well<br />
as BPDE exposure there was a significant difference in the apoptotic response between<br />
MPN and control cell lines. Our results reveal that UADT MPN patients have a reduced<br />
apoptotic capacity following an in vitro challenge by γ-radiation and BPDE which can<br />
be associated with risk of multiple primary cancers. We believe that low apoptotic<br />
response in MPN cases could enable cells with DNA damage to accumulate, possibly<br />
conserving mutations in critical genes and inducing carcinogenesis.<br />
There are reports demonstrating a reduced apoptotic capacity in individuals<br />
affected with cancer. A study done by Zheng et al 104 showed a lower level of<br />
apoptosis, along with defects in cell cycle regulation as a biomarker of genetic<br />
susceptibility for salivary and thyroid carcinoma. Similarly, defective apoptotic<br />
response after γ-radiation has been associated with lung cancer risk and is suggested to<br />
be a susceptibility marker 53, 105 . Alteration in the apoptotic pathway as a risk factor for<br />
lung cancer has also been observed by Wang et al. where they assessed cell death after<br />
BPDE exposure 51 . Our results support the hypothesis that defects in apoptotic response<br />
can be attributed as a risk factor for UADT MPN development.<br />
Differential gene expression after γ-radiation exposure<br />
Differences in cellular responses after genotoxic exposure can be attributed to<br />
differential gene expression. Differential expression of genes in important<br />
carcinogenesis pathways can be considered as driving malignant changes 111-113 .<br />
Deregulated expression of DNA repair genes in pathways like nucleotide excision<br />
repair is found to be associated with in lung cancer 111 . A more than 2 fold increased of<br />
risk of head and neck cancer has been observed in individuals expressing lower levels<br />
of nucleotide excision repair genes 112 . Similarly, in a study done on Indian population<br />
reduced expression of DNA repair genes was observed in head and neck cancers 113 .<br />
However most of these studies were done by classical way of selecting known genes in<br />
important pathways already identified to be altered during malignant transformation.<br />
In order to explore the involvement of novel molecules in cancer<br />
predisposition there is a need to measure global gene expression alterations for which<br />
cDNA microarrays provide an obvious method of choice 109, 110 . The association of<br />
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