[Chromatin degradation in the death of thymic lymphocytes induced by radiation or dexamethasone: the necessity for a stage of preliminary proteolysis]. / Degradatsiia khromatina pri gibeli limfotsitov timusa, indutsirovannoi radiatsiei ili deksametazonom: neobkhodimost' étapa predvaritel'nogo proteoliza.

Proteolytic activity in a protein fraction of a rat thymocyte nuclear matrix was found to increase 1-2 h after gamma-irradiation or administration of dexamethazone. Cycloheximide did not prevent the observed protease activation. Neither histons nor thymocyte nuclear matrix proteins were subjected to proteolysis after exposure to radiation or the hormone. Such proteolysis inhibitors as phenylmethylsulfonyl fluorine, trasilol, and partly leupeptine inhibited nuclear DNA degradation in irradiated and dexamethazone treated thymus lymphocytes. In all appearance, this effect was not due to Ca/Mg-dependent endonuclease inactivation. The same was observed in the system of autolytic chromatin degradation in isolated thymocyte nuclei.

[Spontaneous DNA damage and DNA polynucleotide ligase activity in thymocyte populations differing in radiosensitivity]. / Spontannye povrezhdeniia DNK i aktivnost' DNK-polinukleotidligaz v populiatsiiakh timotsitov, razlichaiushchikhsia po radiochuvstvitel'nosti.

Single-strand breaks (SB) in DNA of irradiated thymocytes are first repaired, at a half-recovery period of a few minutes, then the number of breaks rapidly increases indicating that in addition to chromatin endonucleolysis there is an imbalance between the repair enzymes that generate DNA breaks and eliminate them. The rate of SB accumulation in thymocyte fractions, upon incubation of the cells with 1-beta-D-arabinofuranosyl cytosine (AraC) and hydroxyurea (HU), is directly proportional to their radiosensitivity, whereas DNA ligase activity is higher in a fraction of highly radioresistant thymocytes. Chemical compounds that increase the survival rate of irradiated thymocytes decelerate SB accumulation in DNA and sensitivity of cells to AraC and HU. Ineffective substances have no such an effect.

[Degradation of chromatin in thymus lymphocytes during inhibition of repair of spontaneous DNA damage]. / Degradatsiia khromatina v limfotsitakh timusa pri ingibirovanii reparatsii spontannykh povrezhdenii DNK.

Chromatin degradation and cell death were observed after 6-7 h incubation of mouse thymus lymphocytes with 1-beta-D-arabinofuranosylcytosine and hydroxyurea. The time dynamics of both processes was similar. In this case, just as after gamma-irradiation, nucleosomes and their oligomeres were the products of degradation. Puromycin and cycloheximide prevented the toxic action of DNA synthesis inhibitors on thymocytes. It is suggested that the accretion of unrepaired DNA damages to some critical level triggers the process of the internucleosome degradation of chromatin, i.e. implements the program of lymphocyte death.

[The role of spontaneous DNA damage in the radiosensitivity of thymus lymphocytes]. / Rol' spontannykh povrezhdenii DNK v radiochuvstvitel'nosti limfotsitov timusa.

The most radiosensitive thymus cortical lymphocytes are highly sensitive to inhibitors of repair of spontaneous DNA lesions known by endonucleases: this is indicative of different level of injury to cells. The preincubation of cells with chemical inductors of differentiation increases the number of spontaneous lesions in them. The preincubation of thymocytes with concanavalin A removes almost completely the differences in the level of injury.