Views and Suppositions About Malarial Infections in Cancer Development and Progression

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Introduction
In our opinion, the mechanism of action of plasmodium falciparum on target cells is the destruction of the plasma membrane (induction of different types of perforations) and finally the fusion of somatic cells and the development of karyogamy. From the position of karyogamic theory, the action of any carcinogens is not associated directly with the gene apparatus of cells. Alteration of the cell's genome is induced indirectly; that is after the somatic cells' fusion and arising precancerous, tetraploid cell.
As it is known, somatic cells never interact. There is always space between them which is approximately 100-200 Å The balance between attraction and repulsion should be maintained at this interval. If for any reason the interval becomes less than 10Å, the formation of Ca bridges is starting leading to the long-term adhesion of the cell. Intercellular contacts are predominantly determined by two main forces; Van Der Waals positive taxis) and electrostatic (negative taxis) forces contributing to the formation of membrane electric potential. As the rigidity of leucocyte's plasma membranes is higher, it is possible that during the destruction of erythrocytes by plasmodium falciparum in leucocytes damages plasma membranes and pores of definite size, which may promote the process of fusion of somatic cells, may be formed. Larger perforations induce considerable destruction of cells' membranes and the following cytolysis together with the perishing of these cells. It seems that pores in the plasma membrane on the somatic cells formed by the action of plasmodium falciparum, substantially decrease the negative charge of the plasma membrane. Perforations lead to the weakening of the electrostatic forces and enhancement of the Van der Waals forces helping somatic cells to overcome intercellular forces and enter into contact with each other. In the case of prolonged contact adhesion process will start to develop, 4 which frequently especially upon the coincidence of the perforated parts, may serve as a prerequisite to fusion. At this stage, together with multinuclear cellular structures, the binuclear-hetero-or homokaryons-carriers of high carcinogenic potency are formed. As a result of karyogamy, i.e. after synchronous mitosis or simple mechanical assembly of nuclei heterokaryons (or homokaryons) mononuclear hybrid precancerous cells develop, with tetraploid (or hypo tetraploid) set of chromosomes on the initial stage of hybridization. Received as a result of somatic hybridization, the hybrid synkaryon is an initiated, immortal, precancerous cell, which exists in macro organisms indefinitely for a long time. At the initiated stage of its formation, tumor synkaryon possess a tetraploid or hyper tetraploid set of chromosomes. Fusion immediately doubles the number of chromosomes, thereby decreasing the chances that the loss of some chromosomes will kill the hybrid cell(synkaryon of stage 1) Further, in the processes of promotion and tumor progression, after the segregation of some chromosomes, there may arise tumorous cells with aneuploid or even hyperdiploid set of chromosomes. In extremely rare cases, tumorous cells possess even diploid, hypodiploid, or even hyperdiploid sets of chromosomes.
On the promotion stage, after the influence of full carcinogens or promoters on tissue (in our case P agentlasmodium falciparum), where precancerous synkaryons preexist, in these cells the chromosomal aberrations of different types and gene amplifications may arise. One of the conditions in the formation of both precancerous and tumorous cells is quantitative aberrations of chromosomes. After the invasion of Plasmodium falciparum, it seems that lymphoid cells contact with each other, following adhesion and fusion. Plasmodium falciparum has high lymphotropic abilities and is a strong fusogenic agent.In the process of tumor progression, segregation of some chromosomes in the tumorous synkarion, and also the involvement of last cells by means of fusion of a considerable amount of other tumorous cells and normal cells of different types and maturity take place. After this tumorous cells with extreme polymorphism of karyotypes and new abilities, arise. Tumor substrate originates from one synkaryon, or despite its clonal character, in most cases, the tumorous cells of highly morphologic and cytogenetic polymorphism originate.
In distinction from the generally accepted modern views in oncology, which consider that initiated agents influence the cells' genotype, by the karyogamic theory of carcinogenesis, initiated agents in the first instance interact with the cell plasma membranes, inducing their perforations, fusion process, and only then cells somatic hybridization(i.e. quantitative aberrations of chromosomes). 5

Conclusion
Here we are trying to answer one question in oncology from the view of karyogamic theory: How Plasmodium falciparum raises cancer risk? After the invasion by Plasmodium falciparum, the patient develops early morphological changes, in particular fusogenic processes in the lymphoid type of cells. It can be a prerequisite for the production of tumor cells and high incidences of Burkitt's lymphoma. Thus, it could be concluded that plasmodium falciparum can induce cells'malignization by means of somatic hybridization. Consequently, the hybridization of somatic cells represents itself as one of the possible mechanisms of malignant conversion.