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.

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.

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).

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.

The study was supported by grant of the Presidium of Russian Academy of Sciences N15-4-4-23.