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 initial effect of N-methyl-N-nitrosourea (MNU) on doublestranded calf thymus DNA was studied by means of derivative pulse potarography, kinetic formaldehyde method and spectrophotometric denaturation curves. In the first 30 rain of the reaction it was found that, at a molar ratio MNU : DNA P ----20 : 1, changes in the pulse-polarographic behaviour of DNA took place, while no changes in T m were detected. A higher reactivity of DNA with formaldehyde was observed in the same time interval, when a higher ratio MNU • DNA P (50 : 1) was used. The increase of the pulse-polarographic peak that was observed at room temperature and slightly acid pH, or at neutral pH and elevated (premelting) temperature was explained by a local destabilization of the double helix.Further experiments showed that the initial effects of MNU are strongly dependent on the DNA conformation; the rate of reaction of single-stranded (denatured) DNA was substantially higher. As a consequence of the initial effects of MNU on the double-stranded DNA thermolabile bonds were formed, which resulted in the breakage of sugar-phosphate backbone in the course of DNA heating. The number of single-strand breaks appearing primarily due to the effects of MNU on the double-stranded DNA during the first 30 rain of the reaction was under the limits of detection.Note Added in Proofi After submission of this article for publication a paper appeared [Sequaris, J. M., Reynaud, J. A., Malfoy, B.: J. Electroanal. Chem. 77, 67--72 (1977)] in which the authors used alternating current polarography for the study of DNA methylated by dimethylsulfate. The authors studied only heavily methylated DNA (about 10% of bases methylated) and demonstrated a new polarographic peak connected with the presence of 7-methyldeoxyguanosine in DNA.