CARCINOGENESIS (oncogenesis; Greek onkos weight, tumor + genesis origin, origin; synonym: blastomogenesis, carcinogenesis) — process of emergence and development of a tumor. For an explanation of mechanisms O. various theories and concepts were offered. According to Yu. Kongeym, O. is connected with eliminating in the embryonal period of separate cells or their complexes, to-rye, having ability to proliferation, form rudiments of a tumor. Transformation of such rudiments into a tumor requires easing fiziol, counteractions of surrounding fabric, the essence to-rogo was not clear. Considered Boret (M. of Borst) that rudiments of a tumor are formed not at the expense of an allotopia, and features of exchange and reproduction of cells which resulted in an embryogenesis. According to Ribbert (M. of W. H. Rib-bert), the main reason leading to emergence of a rudiment of a tumor is release of group of cells of normal anatomo-fiziol. bonds both in embryonal, and in postembryonal the period, napr, as a result of an injury or an inflammation. The theory of irritation is connected with a name of R. Virkhov, to-ry pointed to a role of irritation in O. and gave such examples as the carcinoma cutaneum of chimney sweeps described in 1775 by P. Pott, cancer of an under lip at smokers of a tube described in 1795 by S. Th. Soemmerring and other observations. In opinion B. Fischer-Vazeljsa, O. begins with formation of a tumoral rudiment, to-ry can consist of embryonic cells or of group of the «released» cells of an adult organism. The rudiment can malignizirovatsya (to turn into a tumor) as a result of action of various oncogenous agents. The same agents can cause formation of a tumoral rudiment and directly acting on fabric.
In 1926 independently from each other H. N. Petrov and Bauer (K. N. of Bauer) introduced the idea that developing of tumors is result mutations (see) in somatic cells. In favor of the mutational theory of O. the fact that many Oncogenous agents possess mutagen action demonstrated. This theory formed further the basis of widespread idea of the two-phase mechanism O., a cut formulated in 1954 I. Berenblum. According to this representation the first phase O. is initiation — emergence as a result of a mutation of a tumor cell from somatic; the second phase O. is the promotion — development of a tumoral rudiment and the tumor under the influence of additional tumor promoters; e.g., in experimental conditions croton oil has such effect. According to the mutational theory of O. comes suddenly, and further development of a tumor happens due to reproduction of the malignizirovanny cells which already have all tumoral properties. However experimental tumors arise under the influence of oncogenous substances or ionizing radiation after long stage of latency and their emergence is preceded, as a rule, by pretumor changes. The mutational theory of O. is contradicted also by multistaging and gradualness of process of a malignancy, polymorphism of tumor cells, plurality of pretumor changes, existence in some cases of the so-called tumoral field, etc.
O.'s Mnogostadiynost is noted by hl. obr. for the tumors induced by oncogenous substances, hormones, ionizing radiation or by means of plastic plates. Virus O., however is less studied and in the tumors induced by viruses O. Tak is marked out multistaging, the virus of papilloma of rabbits causes originally development of benign tumors — papillomas of skin, inside to-rykh in the course of a malignancy there are secondary clones of malignant carcinomas. The virus of cancer of mammary glands of mice causes formation of high-quality hyperplastic small knots, in to-rykh there can be clones of cells of malignant carcinomas. Viral leukemia at cats develops against the background of acute limfoproliferativny inf. diseases. Long multistage process is emergence of virus lymphoma at mice of the ACRE vyso-koleykozny line. At the same time in the course of O. from not oncogenous endogenous viruses their recombinations result the Oncogenous options of viruses causing malignant thymomas. In most cases at induction of tumors viruses, such as viruses of sarcomas of Raus and Moloni, virus on-liomy, SV40, etc., is observed more or less long stage of latency.
An essential symptom of the spontaneous or induced by oncogenous substances tumors is their monoclonality testimonial of initial developing of a tumor from one cell. It is very probable that not all transformed cells give rise to a tumor. Many of them can regress under the influence of natural antineoplastic resistance of an organism.
In modern ideas of O. the large role is played immunol, by the concept of the Lake. According to L. A. Zilbera, etc. (1948), each tumor has specific antigens, at the same time in the induced and spontaneous tumors they are fabric, in nek-ry tumors embryonic antigens, napr, alpha-fetoprotein appear. The originality of antigenic structure of a tumor can explain change of its reaction to action of the regulating systems of an organism and be the cause of autonomy of tumoral growth (see. Autonomous growth ). An important role in O. is played the increasing atypia of enzymes and changes of cellular membranes. At the beginning of 20 century F. Blumen-thal suggested about existence in tumor cells of special proteins and enzymes. Further it became clear that O. is connected with change of macromolecules of the cells responsible for their growth, reproduction, a differentiation and inheritance of these changes, i.e. with changes of DNA, RNA and the proteins coded by them. An important factor is, apparently, the selection providing preferential reproduction of the changed cells. It is possible that such selection is promoted by smaller sensitivity of tumor cells in comparison with normal to disturbances of conditions of food, tissue respiration, various toxic influences, including and oncogenous substances.
The most changed cells, continuing to breed, give rise to the tumors differing in the increasing autonomy. Such observations formed a basis for a concept about progressions of tumors (see), the cut is characteristic property independence of separate signs of tumoral growth.
The tumor arises, apparently, not directly and not from any normal cells, and only from oncogenous agents, gradually changed, perhaps especially sensitive to action. There is an assumption that the low-differentiated reserve stem cells have such high sensitivity. The series of observations demonstrate multitsentrichny developing of tumors, about plurality of their rudiments. As a rule, these rudiments are in different stages of O., but are located, according to Willis (V. with A. Willis), on one site, to-ry call the tumoral field. The concept of the tumoral field relies on the changes in face skin arising under the influence of long intensive operation of Uv-radiation. The tumoral field can be considered also tissue of mammary glands with multiple sites of a fibrosing adenosis, a mucous membrane of a large intestine with multiple polyps, the site of skin a lab. an animal, to-ry greased with solution of benzpyrene, etc.
Each tumoral rudiment can give the clone of tumor cells. Further natural selection of tumoral clones and probably cells in clones, in connection with a number of conditions of a microenvironment is noted, in a cut future tumor cells grow and breed. At the same time the structure, a structure and reactivity of the surrounding connecting fabric providing formation of a stroma of a tumor and its blood supply is of great importance. The inflammation around the formed tumor in one cases promotes its growth, in others — interferes with it. Expression immunol. reactions the shaft which is formed, as a rule, around O. from connective tissue cells is. Malignancy of the cells and fabrics cultivated out of an organism and also O. in an experiment on a lab. animals, show that in many cells considerable changes of kernels and especially chromosomes are observed. Often arise patol, changes of chromosomes, to-rye were described at the end of 19 century by D. P. Hansemann and are considered as a characteristic sign of an anaplaziya. However it is not found out whether changes of chromosomes are the reason or a consequence of tumoral growth. They are found in tumor cells changeably, their character is various in different tumors.
The island is, as a rule, caused by effect of various oncogenous substances or their combination with virus or other agents. The combination of action of various oncogenous agents with nonspecific, i.e. not oncogenous, factors — kokantserogenez is sometimes noted, to-rogo strengthening of oncogenous effect is caused. E.g., greasing of leather of mice benzpyrene in the dose not sufficient for development of a tumor, and the subsequent putting croton oil leads to strengthening of oncogenous action. In some cases the oncogenous substance entered into an organism can cause development of primary tumors in bodies and fabrics, remote from an injection site. Such tumors were got in lungs, mammary glands, sebaceous glands, etc., e.g., during the greasing of leather of mice by coal tar and chemically pure polycyclic aromatic hydrocarbons. According to Lynch (S. of Lynch), L. M. Shabada (1927, 1928), repeated greasing by coal tar of leather of mice in a lineage caused considerable increase of tumors of lungs. Further in experiences with chemically pure oncogenous substances increase of tumors of a stomach, liver, thyroid gland and other bodies was noted. In 1928. L. By M. Shabad it was suggested that oncogenous substance can be transmitted through milk or a placenta. According to Larsen (S. of Larsen) et al. (1947), introduction to pregnant mice of urethane leads to development in their posterity of adenomas of lungs. A possibility of transition of various oncogenous substances through a placenta and the subsequent their oncogenous action on various fabrics of an embryo are proved on different types a lab. animals. Embryonal fabrics have special sensitivity to oncogenous influences, and the posterity has tumors of the central and peripheral nervous system, a liver, kidneys. In organ cultures of the embryonal fabrics treated to transplacental action of various oncogenous substances emergence focal a pro-bodice-ratov and benign tumors is noted. So, e.g., adenomas of lungs at transplacental influence of benzpyrene or urethane arise in explants already on 2 — the 4th day of cultivation. The transplacental oncogenous effect is observed at administration of oncogenous substance in the period of the last third of pregnancy. Its introduction in the period of the first third of pregnancy, as a rule, is pernicious for a germ, and in the second — causes inborn uglinesses. According to Herbst (A. L. Herbst) et al. (1971), numerous cases of cancer of vagina and nek-ry other tumors of the sexual sphere at young women and girls are known, mothers to-rykh accepted high doses of oestrogenic drugs during pregnancy. Means, etc. can have transplacental oncogenous effect professional harm, smoking, nek-ry pharm. In addition to transplacental, transfer of oncogenous substances and viruses through milk of nursing mothers is possible.
The large role in O. is played by Oncogenous viruses, defiant sarcomas, carcinomas and leukoses at different types of animals. The role of viruses in O. at the person is insufficiently studied. Very probable consider participation of a gerpesopodobny virus of Epstayn — Barre in development of a lymphoma of Berkitt and a nasopharyngeal carcinoma.
Discovery of endogenous oncogenous viruses raised a question of their role in developing of the spontaneous and induced by oncogenous substances tumors. At the same time the part of activators of endogenous oncogenous viruses was assigned to physical and chemical impacts. However these viruses appeared incapable to induce tumors. Such activity arose at them only as a result of a recombination of two types of endogenous viruses — what and ksenotropny on the gene controlling coat proteins of a virus. Recombinant forms of an endogenous virus gained ability to active replication in fabrics where they usually do not breed, and led to emergence of T-cellular lymphoma. Endogenous onkovirusa are not found in the person.
Transformation of cells the oncogenous in vitro viruses is important for the analysis of mechanisms O.
The virus of a polioma and SV40, Oncogenous adenoviruses and nek-ry sarkomatozny oncornaviruses, such as viruses of sarcomas of Raus, Moloni and nek-ry others belong to such viruses. Viruses of a leukosis of mice and birds possess the transforming action on cells of in vitro less often. At the same time fixing of a virus genome or its part in a genome of a cell — integration of virus and cellular genomes is essential. It is necessary also that the oncogene, i.e. the gene responsible for transformation of cells was a part of a virus genome. Oncogenes and their proteinaceous products are identified for many oncogenous viruses causing sarcomas, carcinomas or leukoses.
Developing of tumors is local process, but is undoubted, depends on an organism in general since represents result patol, transformations and growths of cells of an organism. Naturally therefore that in O. the great value is attached to obshchere-guliruyushchy systems of an organism.
To studying of a role of a nervous system in O. it was paid much attention. Experiences on mice showed that at animals with the mobile, actively adapting, nervous processes both the spontaneous, and caused onkogennsh substances of a tumor arise in smaller percent of cases and in later terms, than at mice with an inert nervous system. For development of malignant tumors change of neurohumoral regulation of trophic processes in an organism matters. In O., as well as in anything another patol, the process proceeding in an organism, disturbance of the regulating influences of a nervous system can affect a metabolism, endocrine balance, on a trophicity and blood supply of fabrics and an indirect way to affect results of effect of oncogenous substances. It is impossible to attribute to a nervous system a specific role in O.; the proof of it is the possibility of a malignancy of fabrics out of an organism.
It is known that restriction of quantity and caloric content of food leads to reduction of frequency of cancer cases and to later developing of experimental tumors. Increase and strengthening of growth of tumors is observed at increase in contents in food of lipids, in particular cholesterol. To same conducts avitaminosis, especially reduction in food of content of vitamin A, Riboflavinum, and especially ascorbic to - you. Developing of tumors of a liver at rats is of great interest, in a diet to-rykh the content of sincaline is sharply reduced. Increase of cancer cases of a liver in South Africa and in the nek-ry Regions of Southeast Asia can also be connected, apparently, with insufficiency of sincaline and other disturbances of food. Disbolism at O. connect with features biochemical, disturbances of enzymatic processes and, apparently, the nature of synthesis of proteins.
Disturbances of activity of hemadens are of great importance in an origin of many tumors. It is possible to distinguish tumors, in O. to-rykh a crucial role plays an endocrine imbalance, and those tumors, to-rykh endocrine frustration affect an origin to a lesser extent (leukoses, tumors of kidneys). In all cases dishormonal tumors arise indirectly, as a result of difficult mechanisms. In some cases disruptions of communication are their cornerstone, in to-rykh a big role plays a hypophysis.
The ideas that cancer cannot arise in an organism with the kept defense reactions were repeatedly introduced. Attempts to get into an essence of these reactions, to use their absence for diagnosis of tumors, and, above all to stimulate them for suppression or at least O.'s delay, were made long ago. Especially great attention is paid to studying immunol, reactions at O. and tumors, in particular for a role of T - and V-lymphocytes.
Activity of a nervous system, biochemical, processes and a metabolism, protective systems of an organism, degree of order of body tissues to oncogenous agents are defined by a genotype. The role of heredity is shown only in nek-ry, special, exceptional cases of O. (bilateral retinoblastomas of a retina, nek-ry neuroblastomas, Vilms's tumor at children, a pigmental xeroderma, multiple polyposes of a large intestine). However in all these cases not the tumor but only predisposition to its emergence is inherited.
The lake depends on character, a dose and duration of action of an oncogenous factor, to-ry it caused, napr, strong Oncogenous substances cause tumors and their more malignant forms in rather short terms. However the less intensively oncogenous influence, the is more role of other general and local factors, to-rye can modify, change O. Primer of the local modifying factor inflammatory process in the field of primary appendix of the oncogenous agent can be. The inflammation, in particular acute purulent, can slow down, stop O., even to destroy a rudiment of a tumor, however in some cases hron, the productive inflammation can promote the Lake. Dishormonal shifts, changes of a metabolism, age, various fiziol, states, napr, pregnancy, a lactation can exert the general modifying impacts on O.
In the organism there can be endogenous Oncogenous substances, napr, as a result of disbolism.
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