LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...
LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...
LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...
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S. <strong>Ghosh</strong>, M. Krishna / Mutation Research 729 (2012) 61–72 65<br />
Fig. 3. Gene expression of ATM, DNA-PK, Rad52 and MLH1 in A549 cells irradiated with different doses of -radiation. Total RNA from A549 cells was isolated and reverse<br />
transcribed 4 h after irradiation. RT-PCR analysis of ATM, DNA-PK, Rad52 and MLH1 genes was carried out as described in Section 2. PCR products were resolved on 1.5%<br />
agarose gels containing ethidium bromide. -Actin gene expression in each group was used as an internal control. Ratio of intensities of (A) ATM, (B) DNA-PK, (C) Rad52 and<br />
(D) MLH1 band to that of respective -actin band as quantified from gel pictures are shown above each gel picture. Key: Lane 1, control unirradiated A549 cell line; Lane 2,<br />
2 Gy acute dose (single dose that was delivered in each fraction) of 60 Co -irradiation; Lane 3, 2 Gy of 60 Co -irradiation daily over a period of 5 days; Lane 4, 10 Gy acute<br />
(which is the sum total of all the fraction) 60 Co -irradiation. Data represent means ± SE of three independent experiments; significantly different from unirradiated controls:<br />
*P < 0.05, **P < 0.01.<br />
study human lung adenocarcinoma A549 cells were found to be<br />
more radioresistant if 10 Gy dose was delivered as 5 fractions of<br />
2 Gy dose. Although fractionation is supposed to play an important<br />
role in inducing an adaptive response and deciding the fate of cells,<br />
the mechanism by which it does so can be many and innumerable<br />
factors could be responsible. DNA microarray analysis is a powerful<br />
tool for obtaining comprehensive information concerning expression<br />
of thousands of genes in cancer cells [45] DNA microarray<br />
analysis revealed variable expression of many genes. Up-regulated<br />
genes in A549 cells exposed to fractionated irradiation were associated<br />
with p53 signaling pathway, cytokine-cytokine receptor<br />
interaction, hematopoietic cell lineage, toll-like receptor signaling<br />
pathway, Jak-STAT signaling pathway, MAPK signaling pathway,<br />
cell-cycle check point, B cell receptor signaling pathway, DNA<br />
replication, mismatch repair, homologous recombination. Toll-like<br />
receptor signaling pathway is responsible for survival and proliferation<br />
of the cells [46]. The Janus kinase-signal transducer and<br />
activator of transcription (JAK-STAT) pathway mediate signaling<br />
by cytokines, which control survival, proliferation and differentiation<br />
of several cell types [47]. MAPK signaling pathways are<br />
known to be involved in various processes of growth, differentiation<br />
and cell death [48]. Most of the pathways which were<br />
up-regulated in A549 cells exposed to fractionated irradiation in<br />
all comparisons were associated with the survival or repair of<br />
the A549 cells. This indicates that fractionated irradiation could<br />
induce up-regulation of survival/repair related pathways in cancer<br />
cells.<br />
To the authors’ knowledge, this is the first report indicating<br />
the differential gene expression profiles of A549 cells<br />
exposed to fractionated irradiation. Previous reports concerning