Four hypotheses on mitochondria's role in the development and regulation of oxidative stress in the normal state, cell pathology and reversion of tumor cells.

The biological evolution has resulted in adaptation of both unicellular and multicellular organisms to negative effect of excessive O2 in reply to gradual increase of free oxygen (O2) contents in the earth atmosphere. This adaptation has led to formation of various antioxidant systems in the organism. Such system within the cell has hierarchic structure and is represented by at least than three levels of protection: antioxygene, antiradical and antiperoxide. The first and most effective antioxidant level is represented as mitochondrial respiration able to perform several functions. One of these functions is antioxygene since the very the mitochondria's capability to be a main O2 consumer in the cell provides for low but sufficient for respiration and energy supply levels of O2 partial pressure and dependent concentrations of active O2 forms. The latters, being signal molecules at certain values, modify regular and synthetic processes in the cells either directly or indirectly. This is the possibility for mitochondria to more extensively affect the intracellular processes than simply produce ATP. In case of defective of the cell first protection line the hyperoxia starts due to poor utilization of the incoming O2. Change in mitochondria's "capacity" (quantity, size and maturity level of mitochondria) anyway occurring in the cells are an efficient way of regulation of the oxy-peroxide condition (oxidative stress) and related signal channels. The relationship between changes in the condition of cells, i.e. from their normal state to different pathologic forms, and growing disbalance Delta(PO-AO) between its pro-oxygen (PO) and anti-oxygen (AO) components has been assumed. It is expected that during the evolution the cell could have supposedly acquired a sequence of "specialized" Delta(PO-AO) disbalances. Each sequence needs to implement a certain set of biochemical processes. The probability of Delta(PO-AO) disbalance gradation with specification of their value ranges has been determined. These ranges identify or impact certain cell state, namely proliferation of normal cell (oxidative mitogenesis), ageing, A1 apoptosis, carcinogenesis, A2 apoptosis, and oxidative cytolysis. The cited assumption allows us to: (1) explain reverse dependence of cell proliferation due to the level of their differentiation, increase in the amount and activity of mitochondria as an indispensable condition for the disbalance shift towards differentiation, (2) bring up the idea that regress of the cells, and in particular tumour cells, directly results from the Delta(PO-AO) disbalance decrease to certain levels under the influence of reverse inductors, (3) explain relatively easy and frequent embryonic and stem cells malignancy, and also their reversal normalization. These phenomena occur due to small number and/or size of mitochondria in the designated cells. To verify the above mentioned hypotheses it is primarily necessary to be able to stimulate and slow down the mitochondria biogenesis in the embryonic, stem, ageing, cancer and other cells.

[The combined magnetoradiotherapy of breast cancer]. / Kombinirovannaia magnitoluchevaia terapiia raka molochnoi zhelezy.

Preoperative magnetoradiation therapy of stage II-III breast cancer patients was followed by pronounced regression of tumor and axillary lymph node metastases in all cases. The treatment modality had been previously substantiated by establishing the optimal sequence and time intervals for magnetic and radiation fields. Complete regression of primary tumor and metastases verified by histologic and cytologic examination of surgical and biopsy material was observed in 20%. The best results were obtained for edematous-infiltrative form of cancer. In the control group (radiation alone), regression of tumor was only slight, nor did lymph node metastases regress. Magnetoradiation therapy did not involve either immediate or delayed adverse side-effects.

[Variability and inheritability of the "level of endogenous SH groups" trait in cell and clone populations of transplantable rat tumors]. / Izmenchivost' i nasleduemost' priznaka "uroven' éndogennykh SH-grupp" v populiatsiiakh kletok i klonov transplantiruemykh opukholei u krys

Heterogeneity of cell and clone populations in various histogenesis of rat tumours has been studied by the content of the endogenic SH-groups. The distribution of the ovary tumour cells and their clone lines, as well as lung clones of the sublines of rat rhabdomyosarcoma RA-2 as to the content of endogenic SH-groups is of persistent and monopeak character. Modal classes are well expressed, in several clone lines variability of the cell composition is higher than in the initial population. In this case the distribution of cells as to the SH-group content differs from the normal (asymmetrically). The level of SH-groups in the RA-2 rat subclone in 71 lung clones positively correlates with the level in hypodermic transplants. So, the heterogeneity of the clone populations as to the amount of SH-groups depends on both the genetic interclonal differences and fluctuations of the environmental factors.

[Radiosensitivity of tumor cells as a quantitative trait with a facultative threshold manifestation]. / Radiochuvstvitel'nost' opukholevykh kletok kak kolichestvennyi priznak s fakul'tativnym porogovym proiavleniem.

Study in the variability and heritability of the "radiosensitivity" character in clone populations of rhabdomyosarcoma RA-2 and carcinosarcoma K10 in rats has shown a hereditary heterogeneity of the clonogenic tumour cell populations by the given character and probability of the facultative threshold display.

[Sarcolysine sensitivity of the progeny of the clonogenic cells of rat rhabdomyosarcoma RA-2]. / Chuvstvitel'nost' k sarkolizinu potomstva klonogennykh kletok rabdomiosarkomy RA-2 krys.

Cells of rat rhabdomyosarcoma Ra-2 inoculated intravenously were trapped only in lungs and formed progressively growing monoclonal metastases. The population of clones was sensitive to the sarcolysin treatment (10-30 mg/kg) at all stages of clone formations (from 1 to 14 days). The drug acted by two ways: by the reduction of the number of clones and by the clone growth rate inhibition. Independent variability of both types of the clone sensitivity resulted in the highly heterogeneous response of clone populations to the sarcolysin treatment.

[Patterns of the variation in kinetic growth parameters in populations of clones of transplantable rat tumors in vivo]. / Zakonomernosti varirovaniia kineticheskikh parametrov rosta v populiatsiiakh klonov perevivnykh opukholei krys in vivo.

Clones of the rat transplantable tumors: Walker's carcinosarcoma, rhabdomyosarcoma RA-2 and ovary carcinoma, were obtained by means of the lung colony technique and then transplanted subcutaneously and intraperitoneally. Growth parameters of the clones and their transplantants were measured (T, phi = ln2/T, V1). All the tumors gave populations of clones and transplantants with high variability of growth kinetics. There was a positive correlation between growth kinetics of the I and II generation transplantants, and the selection by growth kinetic parameters proved effective. The growth kinetic parameters seem to be quantitative indices with relatively low heritability, and populations of tumor clonogenic cells are heritably heterogeneous by their growth kinetic parameters.

[Results of selection for affinity in cell populations of rat transplantable tumors]. / Rezul'taty otbora na affinitet v kletochnykh populiatsiiakh nekotorykh transplantruemykh opukholei krys.

Results of selection for the affinity for lung tissue in cells of three transplanted tumors of the rat are given. Tumor cell suspensions were injected intravenously-intraperitoneally or subcutaneously-intravenously (the clonal line -- clone circuit), or intravenously-intravenously (the clone-clone circuit). The efficiency of the method has been shown in the cases of the Worker carcinoma and of a 20-methylcholantren-induced rhabdosarcoma. A 10-fold recloning of cells of the ovary ascite tumor failed to increase their affinity for the lung tissue. It is suggested that a hereditary heterogeneity with the trait "the affinity for lung tissue" may be characteristic of tumor cell populations.