[Study of the dynamics repair of DNA damage caused by N-methyl-N-nitrosourea during activated NAD biosynthesis in rat liver].

Dynamics of the DNA main reparative reactions was studied in rat liver tissue after N-methyl-N-nitrose urea treatment and simultaneous stimulation of NAD biosynthesis in order to evaluate the interrelationship between DNA repair and poly-ADP-ribosylation. Treatment of liver tissue with the mutagen was followed by the preparations incubation in Hanks solution within 30 min at 37 degrees. During the initial steps of restoration an increase in amount of DNA breaks proved to occur in liver tissue of the experimental animals as compared with controls; these deteriorations were decreased down to initial level to the final steps of incubation, while content of breaks in single-strand DNA remained to be high in liver tissue of control animals.

[Interconnection of poly-ADP-ribosylation of histones and NAD level in rat liver during repair of induced DNA damage].

The changes in the DNA single strands induced by MNU and the levels of poly(ADP)ribosylation of the histone fractions have been studied under conditions of increased NAD content in rat liver during the recovery incubation of tissue in Hank's solution at 37 degrees C. In the presence of high (in the physiological range) NAD concentrations the DNA repair was more active in comparison with the control. This process was accompanied by activation of poly(ADP)ribosylation of predominantly core histone fractions.

[Interaction between NAD level and rate of repair of induced DNA breaks in rat liver nuclei].

Within 3 hrs after administration of NAD into rats at a dose of 500 mg/kg of body mass more than a 3-fold increase in content of the nicotinamide in liver tissue, an increase in output of acid soluble material from DNA by 28%, 3-fold activation of the DNA reparative synthesis simultaneously with a decrease in NAD-pyrophosphorylase activity by 31% in liver tissue were detected during reparation of the DNA breaks induced after incubation with ethidium bromide under conditions of NAD excess in liver tissue. Distinct decrease in content of NAD as well as in activity of poly(ADP-ribose) polymerase was found in rat liver nuclei of both control and experimental animals during incubation of liver tissue with ethidium bromide. The rate of the DNA reparative synthesis was shown to correlate directly with the poly(ADP-ribose) polymerase activity and with the content of NAD in liver tissue.

[Features of poly-ADP-ribosylation and chromatin structure under conditions of varying NAD content in the rat liver].

It is shown that nicotinamide-induced in vivo stimulation of NAD biosynthesis in the liver nuclei of rats causes a decrease of the DNA sensitivity to treatment with DNAse I under conditions of weak hydrolysis. When rats are given synthetic vitamin PP-deprived food, the NAD level in the liver falls down to 40% and a great number of DNAse I-hypersensitive chromatin sites appear. A 24% decrease in the level of poly-ADP-ribosylation of total histones in comparison with the control has been observed with hypovitaminosis.

[NAD participation in protecting DNA from damaging factors].

It was found that autolytic degradation of DNA during the isolation of nuclei under conditions of an in situ stimulated NAD biosynthesis is decreased to 2.5% in comparison with 5.2% in control.

[ADP-ribosylation of histones and NAD-pyrophosphorylase activity of chicken liver nuclei during induction of DNA damage].

The rate of [14C]NAD incorporation into chicken liver nuclear histones was studied under conditions of DNA damage by N-methyl-N-nitrosourea and pancreatic DNAase I. With an increase in N-methyl-N-nitrosourea concentration from 8.5 X 10(-2) to 34.

[Dependence of ADP-ribosylation of histones of chicken liver nuclei on the intranuclear content of NAD].

The dependence of ADP-ribosylation of chicken liver nuclear histones on NAD concentration in the nuclei was studied under conditions of stimulation of coenzyme synthesis by the nicotinamide and nicotinic acid as well as upon addition of various concentrations of the [Ado-U-14C]NAD nuclei to the incubation mixture. In the first case, the rate of [Ado-U-14C]NAD incorporation into the histones was decreased due to the dilution of the label by the de novo synthesized NAD. The amount of the latter formed under effects of nicotinic acid and nicotinamide increased, correspondingly, from 2,2 X 10(-5) mmol up to 4.

[ADP-ribosylation of histones of the chicken liver nucleus at different rates of glycohydrolase hydrolysis of NAD].

The rate of incorporation of nicotinamide-[adenosine-U-14C]adenine dinucleotide [( Ado-U-14C]NAD) into histones and the poly(ADPR) polymerase activity of chromatin suggest that the NAD-dependent ADP-ribosylation of histones depends on the rate of NAD hydrolysis by glycohydrolase in chicken liver nuclei. With a rise in the NAD-glycohydrolase activity after treatment of nuclei with Triton X-100 the synthesis of poly(ADP-ribose) via the poly(ADPR)polymerase reaction is augmented, as a result of which the rate of [Ado-U-14C]NAD incorporation into total histones is increased. On the contrary, the decrease of NAD-glycohydrolase hydrolysis after treatment of nuclei with SDS lowers the poly(ADPR)polymerase activity and [Ado-U-14C]NAD incorporation into histones.