The role of metals in the initiation and the development of malignant transformation

Abstract The concentration of metal ions in DNA molecules of a malignant growth is higher than in the norm. The genetic consequences appearing in the DNA molecule as a result of mutations of certain type and of the penetration of metal ions into its structure are considered. The present state of investigation of metal influence upon the structural and thermodynamic properties of DNA, histones and chromatin in the norm and in the malignant transformation is considered. Metals endogen-bound with DNA leave the latter susceptible to the influence of X-rays and certain antitumor preparations. The change in the physical properties (electronic density distribution, thermostability) of DNA, histones and their complexes in the case of cancer are interpreted from the view-point of the influence of endogen-bound metal ions on the structure and cooperative properties of these molecules. The change of dipole moments of DNA sites after the incorporation of certain bivalent metal ions has been established using computation methods. The change in histone structure under the influence of metals has been demonstrated experimentally using X-ray diffraction and spectral methods. The predicted changes in chromatin structure and thermodynamic properties under the influence of metal ions have been confirmed by direct calorimetric and spectral investigations. A general analysis of the available data is given. The program of investigations required in this field is laid out.