[Analysis of the role of DNA repair, regulation of cell cycle and apoptosis in the radiation-induced adaptive response of mammalian cells].

In according with the mechanism for an adaptive response (AR) offered in [Bodnarchuk I.A.//Radiat. biologiya. Radioecologiya. 2002. V. 42. No. 1. P. 36-43], the low-dose irradiation of mammalian cells leads to the activation of such enzymes as Ras, ceramid-activated protein kinase, phospholipase C (PL C) and phosphatidilinostol 3-kinase (PI 3-K). All of them initiate apoptosis and eliminate the most radiosensitive cells form the population before the damaging irradiation. The function of PL C and PI 3-K accompanied by protein kinase C (PK C) activation. PK C activates transcription of the poly(ADP-ribose)polymerase (PARP) gene and DNA polymerase beta gene, and makes posttranslation activation of apurinic/apyrimidinic endonuclease APE, which are participating in the base excision repair (BER). PK C, APE and PARP activate the transcription factor p53, PK C and APE also activate the transcription factor AP-1, AP-1 and p53 take part in the initiation of nucleotide excision reapir (NER). The function of BER, NER and p53 after the damaging irradiation is accompanied by the G1-arrest of cell cycle progression. During G1-arrest there is p53-dependent activation of nonhomologous ends joining (NHEJ) and the inhibition of homologous recombination repair (HRR) of the DNA double-strand breaks takes place. Passing through the NHEJ the cells will outgo from G1-arrest and follow by HRR. AP-1 takes part in outgoing of cells from G1-arrest. So, the preliminary low-dose irradiation causes the decrease of quantity of cells died apoptotically after damaging irradiation as a result of inability to overcome G1-arrest. Thus, AR is the combination of processes: the removal of radiosensitive subpopulation of cells, and/or the activation of DNA repair, and/or the increase of cells ability to overcome the cell cycle delay.