LIFE09200604007 Tabish - Homi Bhabha National Institute

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