[Preirradiation heat shock protein induction increases cellular radioresistance].

It was studied how does the transcriptional stress response and the heat shock protein (HSP) overexpression affect cellular radioresistance. For this purpose, normal murine fibroblasts and fibroblasts devoid of HSF1-gene (HSF1 is a transcriptional factor initiating stress-responsive HSP expression) were compared. Some cell samples were infected with specific vectors for expression of the constitutively active (mutant) HSF1 or individual HSP (HSP70, HSP56, HSP27). It was found that heat stress (43 degrees C, 30 min) increased the HSP level in normal fibroblasts and improved their survival following exposure to gamma-radiation, with both the effects being suppressed by quercetin (an inhibitor of HSF1-mediated HSP induction). In the HSF1-deprived cells, heat stress caused neither the up-regulation of HSP levels nor the enhancement of radioresistance, although both the effects were well manifested following the active HSF1 expression in those cells. The vector-induced over-expression of HSP70 or/and HSP27 equally enhanced the radioresistance in both cell cultures infected.

[Thymodepressin protects murine bone marrow CFU-S from the hyperthermic damage].

Was studied the influence of the Thymodepressin (dipeptide D-iEW--a new Russian immuno- and haemodepressant), on the hyperthermic sensitivity of haemopoietic precursors (CFU-S) and tumor model cells (EL-4 and Rauscher leukaemia). It was determined, that the injection of the Thymodepressin to donor mice, or the incubation with the preparation of the marrowy cells of normal mice provides the increasing of the CFU-S resistance to the following heating (43 degrees C). On the contrary, Thymodepressin-treated tumor cells became even more heat-sensitive. The data show that Thymodepressin can be useful for protection the haemopoietic precursors not only from radiation and chemotherapy, as it was shown earlier, but also from the hyperthermy.

[Postradiation recovery of hematopoiesis in mice affected by Neogen (IEW)]. / Postradiatsionnoe vosstanovlenie krovetvoreniia u myshei pod vliianiem neogena (IEW).

The effect of the synthetic peptide IEW (Neogen) with immunomodulating properties on postradiation recovery of haemopoiesis was investigated. We have shown that Neogen is a potential stimulator of haemopoiesis. The administration of Neogen after irradiation shortened duration of period of the recovery of the compartment of CFU-S-8 and the amount of bone marrow cells. The comparision of the effects of Neogen and GM-CSF (Leucomax) and G-CSF (Granocyte 34) have shown that the targets for these agents are probably different: polypotent CFU-S-for Neogen, and CFU-GM-for GM-CFS. Based on the results, we suggested the mechanism of Neogen effects on heamopoiesis.

[The protective effect of thermal treatment before irradiation on CFUs from bone marrow of mice: a potential involvement of heat shock proteins]. / Zashchitnyi éffekt predradiatsionnoi termicheskoi obrabotki myshei na KOEs ikh kostnogo mozga: vozmozhnoe uchastie belkov teplovogo shoka.

It was studied on mice how prior whole body hyperthemia affects a colony-forming ability of bone marrow after gamma-irradiation. It was found that heating of the animals (42 degrees C, 10 min) 18-22 h before their total irradiation (4 Gy) increases 2-fold the level of CFUs8 and CFUs12 determined in the spleen exotest. The induced radioresistance correlated with accumulation of heat shock proteins, HSP70 and HSP25, in tissues of preheated mice. Injection of quercetin (a selective inhibitor of the heat shock protein synthesis) 0.5 h before the heating fully abolished both the subsequent heat shock protein accumulation and the rise in CFUs populations as compared with control. It is suggested that heat shock proteins, whose expression increases in response to hyperthermia, can play a role of endogenous radioprotectors. Possible mechanisms of their protective action under irradiation are discussed.

[Lack of serum causes apoptosis of thymocytes not requiring protein synthesis and ATP generation]. / Lishenie syvorotki vyzyvaet apoptoz timotsitov, ne trebuiushchii sinteaz belka i generatsii ATP.

Incubation of rat thymocytes in serum-free media was found to result in their apoptotic death characterized by internucleosomal DNA fragmentation, nuclear pyknosis and subsequent irreversible plasma membrane damage. As in the case of glucocorticoid (hydrocortisone)-induced apoptosis, DNA fragmentation under serum withdrawal was suppressed by endonuclease inhibitors (Zn2+ and spermine). At the same time, protein synthesis inhibitors (cycloheximide and puromycin) failed to block the apoptosis induced by serum withdrawal but inhibited the hydrocortisone-induced apoptosis. Various inhibitors of oxidative phosphorylation (uncoupler, rotenone, oligomycin), causing sharp decrease in cellular ATP did not suppress DNA fragmentation, whereas thymocyte plasma membrane damage accelerated under their effect. The results obtained indicate that intact thymocytes contain all the components of the apoptotic system; however, in the absence of apoptotic stimuli (e.g., hydrocortisone) the system is blocked by some growth factors of serum origin. Serum withdrawal is sufficient by itself to induce apoptosis and does not require the synthesis of special proteins.