The ionizing radiation damages DNA and cellular macromolecules directly or
via production of reactive oxygen species. A number of mechanisms protect
cell from impact of ionizing radiation. The purpose of this work was to
investigate the role of cellular stress-resistance mechanisms including
DNA repair, DNA damage response, detoxification of free radicals, and heat
shock response in Drosophila melanogaster resistance to irradiation and
longevity.<br /><br />
We analyzed the effect of ionizing radiation on the level of expression of
stress response genes, and the lifespan of wild-type Drosophila
melanogaster laboratory line. To elucidate the role of stress response
genes in longevity we used mutant lines, that were defected in stress
response genes, lines with overexpression of
these genes, or flies in which stress signaling pathways were
pharmacologically inhibited.<br /><br />
Results: We found that radiation hormesis, radioadaptive response, and
hyperradiosensitivity can be observed not only in cell cultures but also
at the organism level of Drosophila melanogaster by integral indicators
such as lifespan. We also showed that the reaction of an organism to
irradiation is determined by cellular mechanisms of stress
resistance (DNA repair, DNA damage response, detoxification of free
radicals, and heat shock response).<br /><br />
Thus, we investigated the roles of some components of cell stress
signaling pathways in the lifespan alteration after the irradiation. We
found that despite low-dose
irradiation affects the level of genes expression predominantly
stochastically, the mutations in stress response genes, pharmacological
inhibition of their products or genes
overexpression play crucial role in radioresistance and lifespan.
<br /><br />
The study was supported by grant of the Presidium of Russian Academy of
Sciences N15-4-4-23.