CHALONES (option: halona; grech to weaken chalaino) — the substances which are specifically suppressing cell division. The possibility of their use for strengthening of effect of cytostatic drugs and the ionizing radiation at treatment of malignant new growths is supposed.
To. are opened in 1956 by H. Saetren who established that water extracts of a liver and kidneys are tkanespetsifichno capable to inhibit mitotic activity in these bodies at their regeneration. Later To. were found in epidermis of skin, in lungs, a stomach, intestines, a gullet, grease and sweat glands, a crystalline lens, smooth muscle fibers of arteries, in testicles, granulocytes, lymphocytes, erythrocytes, fibroblasts, etc.
According to the available data, all To — water-soluble simple proteins or glycoproteins, pitches, it is powerful (weighing) within 2 — 150 thousand and more, 70 — 80% are besieged by alcohol, keep biol, activity in the lyophilized state, not to dialysis yutsyatsya, termolabilna, the majority them is inactivated by proteolytic enzymes.
It is established that for To. first of all tkanespetsifichesky influence on cell fission and synthesis of DNA and lack of specific specificity is characteristic. On the example of granulotsitarny, lymphocytic and erythrocyte types K. cellular specificity of their action is shown. Cytotoxic influence To. it is not revealed.
One of manifestations of action To. consists in short-term braking of the introduction of cells in a mitosis from the phase G2 of a mitotic cycle (see. Cell , Mitosis ). The premitotic inhibition can reach high degree. This effect caused by single introduction To., we will turn as further there occurs normalization of mitotic activity. Besides, it is shown that To, inhibit transition of cells from a Gx-phase in 5 phase of a mitotic cycle and can influence processes of synthesis of DNA in 5 phase. Presintetichesky inhibition also not for a long time. Thus, in a mitotic cycle there are two «points» sensitive to K. Eto's action — transition of cells from G1-in a S-phase and from G2-in the M-phase. On a nek-eye to data, epidermal To. consists of two components, one of which acts on G2 phase of the mitotic cycle G2 chalone) and another is produced by basal cells of epidermis, and — on G1 phase of G1 chalone), and formed in the differentiated epidermal cells. Marx (F. Marks, 1973) established that G2 chalone of cells of epidermis has a pier. the weight of 30 — 40 thousand, is easily inactivated by heating and proteolytic enzymes, its action depends on presence of adrenaline whereas G1 chalone is characterized by higher a pier. it is powerful (100 — 300 thousand), bigger resistance to heating and proteolytic enzymes and smaller dependence on adrenaline.
Braking of a mitosis epidermal To. occurs only in the presence of adrenaline, and this effect amplifies corticosteroid hormones. On this basis it is supposed that mitotic activity in epidermis is regulated chalone-adrenalinovym by a complex.
The mechanism of effect of chalones is insufficiently clear. Voorkhes's representation (J. Voorhees, 1973) about influence is the most probable To. on contents in cells of cyclic AMF (see. Adenozinfosforny acids ) through interaction with specific receptors on a surface of a cellular membrane.
According to other views, To. affect the gene device of a cell, and it is possible, a differentiation of a cell.
Thus, To. the important role in regulation of cell fission belongs. However not only inhibitor, but also the stimulator of cellular proliferation possessing tkanespetsifichesky action and obnaruzhivamy in blood serum take part in these processes. On this basis there was a representation about chalone-antikeylonnoy to the control system of cell fission. Availability of anti-chalones, the Crimea is peculiar opposite To. influence, is shown concerning a number of fabrics and cells (a liver, granulocytes, fibroblasts, etc.). Believe that daily allowance biol, rhythms of cell fission in some fabrics (epidermis) are caused by the similar mechanism of regulation.
In 1965 Mr. Iversen (O. of H. Iversen) made the assumption of possible disturbance of the keylonny mechanism of regulation of cell fission at development of a tumor. To. are received from an epidermal carcinoma of mice, Guinea pigs and rabbits, from a melanoma of mice and Guinea pigs, from leukemic blood cells (at granulotsitarny and lymphocytic leukemia at the person, and also at mice and rats), from gepatomy-DAB, an astsitny gepatoma of Novikov, from a tumor of a neck of uterus of the person. To. are found in intercellular liquid of experimental astsitny tumors. There are instructions on the fact that in the course of carcinogenesis sensitivity of cells to action decreases To. and, perhaps, their transport from cells on intercellular Wednesday is broken.
The question of use is important To. for suppression of growth of a tumor. Single introduction To. leads to short-term inhibition of proliferative processes. Data on action on growth of a tumor of repeated introduction To. it is not enough. At the same time the Pestilence (U. Mohr) with sotr., 1968, and also Ryutyomaa and Kiviniyemi (T. Rytomaa, To. Kiviniemi, 1969, 1970) observed sharp delay of growth of experimental tumors in these conditions. By A. I. Antokhin, etc. (1976) it is shown that cells of a tumor find a day-night rhythm of sensitivity to action To. Besides, Yu. A. Romanov, etc. (1976) observed that later a nek-swarm time after suppression To. mitotic activity in a tumor there is a wave of synchronization of cell fission. All this, considering tkanespetsifichesky influence To., it can be used for strengthening of action on a tumor of cytostatic drugs and ionizing radiation.
Bibliography: Romanov Yu. A., etc. Tkane-vospetsificheskaya of an ingibition of cellular proliferation in an astsitny tumor of Ehrlich, Bulletin Ekspery, biol, and medical, t. 82, No. 12, page 1477, 1976, bibliogr.; E Ig J about To. Epidermal chalone, Nat. Cancer Inst. MonogT., v. 38, p. 71, 1973; Marks F. A tissue specific factor inhibiting DNA synthesis in mouse epidermis, ibid., p. 79; Rytomaa T. Kiviniemi K. Regression of generalized leukemia in rat induced by the granulocytic chalone, Europ. J. Cancer, v. 6, p. 401, 1970.
Yu. A. Romanov.