Name factors on which transforming action of viruses on a cell depends.

I. Factors which are defined by properties of a virus. So-called structural deficiency of a virus, in particular, is concerned to them. Structurally defective viruses which during duplication and formations of virus particles have lost a part of the genome. They are capable to get into a cell and to be united with its genome; however they are not capable to reproduction. In this case the unique variant of a virus infection is its abortive current which increases probability of transformation of a cell under influence of structurally defective viruses.

Besides for mechanisms of oncogenic actions of viruses the presence or absence in their genome of virus oncogen matters has a great importance.

II. Factors which are defined by properties of cells. They include the presence of corresponding receptors on surfaces of cells, the period of a cellular cycle during which the virus gets into the cell. Integration of a virus genome with cells genome is possible only in a synthetic phase (the S-phase) or during, directly previous it (the end of phase G₁,). In particular such circumstance that high-differentiated cells which have lost ability for duplication are steady against action of oncogenic viruses is explained.

Besides the cell becomes sensitive to oncogenic viruses if in it there are no conditions for synthesis of all proteins of a virus particle. In such conditions the reproduction of a virus and a virus infection is impossible proceeds on abortive to the type at which the probability of transformation of a cell increases. The similar phenomenon has received the name of functional deficiency of a virus.

16.29. What are the viral oncogenes?

Virus oncogenes - are genes of a virus with which functioning transformation of normal cells in tumoral is connected. Proteins - the products of virus oncogenes - break regulation of processes of cellular division and thus cause transformation of a cell (it is an epygenome mechanism of carcinogenesis).

16.30. What are protooncogenes?

Protooncogenes are own genes of cells which bear the information of structure of the proteins which are taking part in regulation of cellular division. Protooncogens are cellular analogues of virus oncogenes.

It?s consider, that virus oncogenes are protooncogens which have gotten in a gene of viruses as a result of long evolution of last. It explains that viruses, passing through cells, can "steal", so take cellular genes with them.

Protooncogens are in all cells. However in one cells they all life are subjected to repression, so "are silent", in others they "work" only during embryogenesis, and in the others - function according to acting of regulation signals.

16.31 How are virus oncogenes and protooncogens classified?

Depending on products, the information about which bear oncogenes viruses and cells protooncogens, they are divided into following groups (fig. 56).

1. Oncogenes, coding factors of growth or their analogues. For example, sis-oncogene of a virus of a sarcoma of monkeys and similar protooncogens of cells code structure of the factor of growth of trombocytes origin.

2. Oncogenes, coding cellular receptors to factors of growth.

For example, oncogen of a virus of hens? leucosis erb-B bears the information on the modified receptor to epydermal factor of growth.

3. Oncogenes which encode tyrosinspecific proteinkinases. As an example can be the scr-oncogen of a virus of Raus sarcoma and corresponding protooncogens of cells.

4. Oncogenes, coding structure of the proteins of transferring the information from receptors of a plasmatic membrane of a cell to a nucleus.

Example is ras-oncogen of a virus of a sarcoma of the rats, bearing the information about cytoplasmatic GTP-connecting protein.

5. Oncogenes, coding structure of nuclear proteins-regulators.

To them, in particular, belong concerns mic-oncogen of a virus of hens myelocytosis.

Products of virus oncogenes are similar to products of protooncogenes, so to own proteins of cells which are taking part in regulation of cellular division. However there are also some differences connected with distinctions in structure of virus oncogenes and protooncogenes. These distinctions make products of virus oncogenes actually oncogenic for a cell.

16.32. What are cellular oncogenes? Name the basic mechanisms of transformation of protooncogenes into cellular oncogenes.

Cellular oncogenes (transforming genes) are protooncogenes which have got ability to transform a cell, so to transform it into tumoral. Carrying of such genes to other, healthy cells causes transformation of the last.

Now existence of following mechanisms of transformation of protooncogenes in cellular oncogenes is proved by.

I. The depression of protooncogen. Can be as a result of violation of structure, and consequently functions of corresponding antioncogen, or mutations in the genes-repressors blocking activity (expression) of protooncogen.

II. Increase of expression of protooncogen It is observed when protein - a product of protooncogen is formed in norm, however it is not enough of it. Under influence of the certain genetic factors formation of such product sometimes essentially raises. The specified phenomenon can be caused by following concrete mechanisms:

?) an amplification of genes (increase in quantity of their spears);

b) chromosomal mutations - translocations;

c) influence of virus promoters and amplifiers (retroviruses which don?t include oncogen operate such way);

d) influence of migrating genes of the cell (transposones).

III. Qualitative changes of protooncogen causing formation of modified product. These changes, as a rule, are caused by dot mutations of protooncogen.

16.33. What are antioncogens?

Antioncogens are cellular genes which products cause repression of protooncogenes.

Loss of antioncogens (deletion) or mutations in them leading formation of inactive products, can have the consequence of depression of protooncogenes and transformation of a cell, so formation of a malignant tumour.

16.34. What molecular mechanisms can underlie in virus oncogenesis?

I. Products of virus oncogen break regulation of cellular division and thus cause transformation of a cell. Such mechanism has received the name epygenome. It is realized in case of action of the viruses containing oncogen in genome. Influence on cells, in particular, is connected with this mechanism of acutetransformate retroviruses.

II. Under action of promoters and amplifiers of the viruses which have taken root in a gene of a cell, there is an activation of own protooncogenes, and they turn into cellular oncogenes, transforming a cell. It is the so-called mutational mechanism of virus carcinogenesis. It is shown in action of the viruses deprived of oncogenes, in particular, slowtransformate retroviruses.

16.35. What molecular mechanisms can be connected carcinogenesis, caused by action of chemical and physical factors?

At action of chemical and physical carcinogenic factors the following molecular changes leading transformation of a cell into tumoral are possible.

1. Dot mutations of protooncogenes.

2. Mutations of antioncogens, adjusting the expression of protooncogenes.

3. Chromosomal aberrations.

4. Formation of defective viruses and receiving oncogen properties.

5. Influence on systems of natural and specific antineoplastic resistance, in particular, development of a condition of immune-depression.

Thus, value of chemical and physical factors as factors of carcinogenesis can consist in their influence: a) on cells, causing formation of cellular oncogenes from protooncogenes (the mutational mechanism of carcinogenesis);b) on viruses, changing their structure and properties; c)on an organism as a whole, breaking mechanisms of antineoplastic protection.

Date: 2016-06-12; view: 95