Inhibition of S-phase progression triggered by UVA-induced ROS does not require a functional DNA damage checkpoint response in mammalian cells

Ultraviolet A (UVA) radiation represents more than 90% of the UV spectrum reaching Earth's surface. Exposure to UV light, especially the UVA part, induces the formation of photoexcited states of cellular photosensitizers with subsequent generation of reactive oxygen species (ROS) leading to damages to membrane lipids, proteins and nucleic acids. Although UVA, unlike UVC and UVB, is poorly absorbed by DNA, it inhibits cell cycle progression, especially during S-phase. In the present study, we examined the role of the DNA damage checkpoint response in UVA-induced inhibition of DNA replication. We provide evidence that UVA delays S-phase in a dose dependent manner and that UVA-irradiated S-phase cells accumulate in G2/M. We show that upon UVA irradiation ATM-, ATR- and p38-dependent signalling pathways are activated, and that Chk1 phosphorylation is ATR/Hus1 dependent while Chk2 phosphorylation is ATM dependent. To assess for a role of these pathways in UVA-induced inhibition of DNA replication, we investigated (i) cell cycle progression of BrdU labelled S-phase cells by flow cytometry and (ii) incorporation of [methyl-(3)H]thymidine, as a marker of DNA replication, in ATM, ATR and p38 proficient and deficient cells. We demonstrate that none of these pathways is required to delay DNA replication in response to UVA, thus ruling out a role of the canonical S-phase checkpoint response in this process. On the contrary, scavenging of UVA-induced reactive oxygen species (ROS) by the antioxidant N-acetyl-l-cystein or depletion of vitamins during UVA exposure significantly restores DNA synthesis. We propose that inhibition of DNA replication is due to impaired replication fork progression, rather as a consequence of UVA-induced oxidative damage to protein than to DNA.     

Significance of endogenous glutathione in realizing the oxygen effect in bone marrow cells

It has been established using hemopoietic bone marrow cells or EHrlich ascites carcinoma cells that endogenous glutathione affects the realization of only those lesions which appear in response to an increase in radioresistance, for example during anoxia. The involvement of glutathione in the realization of the oxygen effect is not limited to the time of irradiation. The effect of glutathione extends to the postirradiation period i. e., it is not determined only by the competition with oxygen for target radicals.     

Effect of triathlon competition on the content of various hormones and the energy substrate of the blood

The effect of triathlon (3.8 km swimming, 180 km biking, 42 km running) and of its short variant (1.5 km swimming, 42 km biking, 14 km running) was studied in 7 and 14 well-trained men, respectively. The level of plasma glucose, total cholesterol, HDL, LDL did not change significantly during the competition. FFA concentration increased significantly (by 439 and 61%, respectively). Triglycerides concentration decreased during the prolonged variant. Both variants of triathlon caused a pronounced rise in the cortisol level and moderate increase in somatotropin and progesterone levels. Testosterone concentration increased during a short variant and decreased during a prolonged one. Insulin and C-peptide levels decreased. All those changes in hormones concentration are consistent with an increased lipolytic activity and, may be, with increased glycolytic activity (maintenance of the normal glucose concentration in blood). The rise in the aldosterone level reflects the homeostatic activity in maintaining electrolyte balance.     

Study of the Compression Dynamics of a Fiber Liner with a Deuterated Target Mounted on the Axis

Plasma Physics Reports - Compression of a fiber array with a deuterated target mounted on its axis is studied at the Angara-5-1 facility (3.5 MA, 100 ns). Cylindrical arrays with an initial...