[The effect of gamma-radiation on the level of labile and strongly bound HMG 1,2 proteins in rat thymus chromatin].
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Biomedical subjects
Publications and source records attributed to G I Revina.
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The ability of polypeptides consisted of aspartic and glutamic acids to inhibit the repair and to promote the formation of unrepaired double-strand DNA breaks and chromosomal aberrations in gamma-ray induced Chinese hamster cells was shown. A complete inhibition of the double-strand DNA breaks repair was observed at the concentrations of 20 mu M/l (polyglutamic acid with molecular weight 2000-15,000 daltons) and 100 mu M/l (aspartylglutamic acid with molecular weight 1500-4500 daltons). Both polypeptides were low toxic at the given concentrations.
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The effects of Pb on the repair of DNA have been studied in the thymocytes of gamma-irradiated mice exposed to diacetate lead in the drinking water (up to 20 mg/l) for 14-50 days. It is found that lead causes no DNA degradation by itself and renders its genotoxic action indirectly, via inhibiting the repair of single-strand DNA breaks induced by acute gamma-irradiation of mice. Genotoxic effect of lead is reversible that becomes evident when exposed animals are maintained on Pb-free drinking water for 1-2 weeks.
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Two groups of proteins of 50-68 kD (A) and 12-14 kD (B) are the components of DNP preparations from rat thymus and liver obtained by washing with 0.075 M NaCl-0.024 M EDTA solution and deproteinization with phenol and dodecylsulfate (SDS). Immediately after irradiation with a dose of 10 Gy, there observed an approximately 1.5-fold increase in the content of only B proteins in the rat thymus fraction precipitated upon treatment with SDS-NaCl. The acidic amino acid content of this fraction and DNP preparation obtained without treatment with SDS amounts to 25 mol%; the ratio to basic amino acids was 1.3-1.4. The comparison of the amino acid content in the above DNP preparation and the "supramolecular DNA" preparation, described in the literature, that was obtained by the same phenol deproteinization and contained about 50 mol% of acidic amino acids, indicates the presence in the "supramolecular DNA" preparation of a component that increases upon irradiation: the component consists almost completely of acidic amino acids and is eliminated completely from the DNP preparation by washing with 0.075 M NaCl-0.024 M EDTA prior to deproteinization. The amino acid composition of the protein fraction A is presented.
Acid polypeptides, synthetic analogues of a natural modifier of lethal effect of radiation, were shown to inhibit double-strand DNA breaks (DSB) repair, to increase irreparable DSB accumulation and to enhance the formation of structural chromosome rearrangements in gamma-irradiated mammalian cells. The authors discuss the possibility of involvement of proteins, that contain amino acid sequences comparable, in length, with a modifier, into radiation formation of irreparable DSB.
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Polypeptide 14C-aspartyl glutamate, a chemical analogue of a natural modified of a lethal effect of radiation, has been synthesized. The modifier was shown to react readily with nucleic acids and proteins of non-irradiated cells: the reaction was considerably enhanced when the modifier was administered simultaneously with radiation of cells. As is known from the literature, a molar concentration of the incorporated polypeptide is considerably lower than the intracellular molar concentration of an active radiosensitizer, BUdr, which produces an effect on mammalian cells comparable with that of polypeptide.
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It has been shown that neither exposure of mice to lead in the drinking water (20 mg/l) for 50 days nor chronic gamma-irradiation of animals (1.5 Gy, 1.3 mGy/h, 50 days) induces single-stranded DNA breaks in thymocytes. Acute gamma-irradiation (1 and 4 Gy) of lead-pretreated mice resulted in an inhibiting of repair of radiation-degraded DNA in thymocytes and in an increasing of the level of DNA lesions detected in erythroblasts of bone marrow by the micronuclear test method. Inhibition of ssDNA break repair in thymocytes caused by lead was not seen upon exposure of mice to combined chronic action of gamma-irradiation and lead. Chronic irradiation did not affect the micronuclei rate increase revealing after acute irradiation of lead-treated mice.