Cellular requirements for deoxyribonucleotide (dNTP) pools during DNA synthesis are related to ensuring of the accuracy of DNA copying during replication and repair. This paper covers some problems on the reactions of dNTP synthesis system in organs of animals against the treatment with DNA-damaging agents. Ribonucleoside diphosphate reductase (NDPR) is the key enzyme for the synthesis of dNTP, since it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. The results obtained show that the rapid and transient increase in NDPR activity in animal organs occurs as cellular response against the treatment with DNA-damaging agents (SOS-type activation). We have also found the intensive radioprotector-stimulated activation of deoxyribonucleotide synthesis as well as DNA and protein synthesis in mice organs within 3 days after the administration of two radioprotectors, indralin and indometaphen, that provide the high animal survival. Our studies suggest that these effects are the most important steps in the protective mechanism of the radioprotectors and are responsible for the high animal survival.
The major task of our investigation is to study electron aspects of interaction of antitumor compounds with the cell components. At present, some nitrosourea derivatives are of significant interest. Methylnitrosourea (MNU) is the most effective antitumor compound used in therapy [ 1-31. This paper gives the results of investigation of MNU electron structure observed by ESR and quantum-chemical methods. To elucidate the nature of MNU chemical activity the nitrosourea derivatives, which are not effective inhibitors of tumor growth, were also studied. The MNU electron structure data proved to be useful in clearing up the mechanism of interaction between MNU and DNA bases. The electron structure of MNU molecule and its ion radicals were calculated by INDO means. In this program the spatial coordinates of all atoms were calculated by ECM from the predetermined values of valency links, valency angles, and dihedral angles. Geometrical parameters of molecules were chosen from the table of standard geometrical parameters [4]. The angles between valency links are: for trihedral hybridization-120", for the tetrahedral one-109.5". All structures are planar with the exception of the following: (i) in molecule I the bond C7-H8 is perpendicular to the molecule plane; the C7-HI0 and C7-H9 bonds make the angle of 30" toward the molecular plane; (ii) in molecule I1 the angle N1C203 is 135"; (iii) in molecule I11 the bond C7-Cio is perpendicular to the molecular plane and the C7-Hs bonds make the angle of 30" toward the molecular plane. The comparison of differences in electron structure of MNU and ,its derivatives should be valid since the geometry of these molecules was chosen on the basis of equal assumptions.I. Methylnitrosourea 11. Nitrosourea (NU)
The electron paramagnetic resonance (EPR) of the triplet excited state of solutions of a series of porphyrins and aromatic amino-acids has been studied at 77°K. It has been shown that for some of the compounds it is possible to observe EPR for transitions with It has been shown that photoreactions in solid solutions of porphyrins and aromatic Reactions of photosensitized deamination of aliphatic amino-acids in solid aqueous A M = & l , &2. amino-acids proceed through the triplet excited state. solutions at 77°K by aromatic compounds have been studied.
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