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Petkova R.,Scientific Technological Service STS Ltd | Tsekov I.,Military Medical Academy | Yemendzhiev H.,University Professor Dr. Assen Zlatarov Burgas | Kalvatchev Z.,Military Medical Academy
Biotechnology and Biotechnological Equipment | Year: 2012

The rate of infection with human papillomavirus (HPV) worldwide is about 80% of the adult population. Anogenital HPV infections are usually transient and cause no lasting damage. In about 15-20% of the cases, however, the HPV infection may persist and in about 1% it may cause transformation of the infected epithelium that might subsequently progress to overt cervical cancer. The hallmark of the malignant transformation is the integration of the viral genome into the host cell genome, resulting in upregulation of the transcription of the viral oncoproteins E6 and E7. The latter are expressed early in the course of the infection, interacting with the major regulators of the cell cycle progression so as to retain the host cell in a state favourable for the replication of the viral genome. Among the crucial cellular partners in the neoplastic transformation of HPV-infected cells are tumour-suppressor proteins such as p53 and pRb, products of protooncogenes such as p21/WAF1, chromatin structure modifiers such as HMGA1, and controllers of the cellular senescence such as the telomerase complex. The high-risk types of HPV seem to have developed mechanisms capable of evading or disabling virtually any defence. Nature has put in place against cancerous transformation, which could account for the high incidence of cervical dysplasia and cervical cancer despite the efforts the modern medicine and healthcare puts into screening programmes, prevention and therapy. The role of the deregulation of the expression of each of these groups of participants in the pathogenesis of activation of persistent dormant infection is reviewed and their impact on the risk for progression to higher grades of cervical intraepithelial neoplasia (CIN) and development of cervical cancer is assessed. Source

Chakarov S.,Sofia University | Petkova R.,Scientific Technological Service STS Ltd | Russev G.C.,Bulgarian Academy of Science
Biotechnology and Biotechnological Equipment | Year: 2012

p53 is a master regulator of the cell cycle, capable of assessing the severity and the scope of damage to the cellular DNA, integrating the signals from the cell under stress and delivering the final decision about the destiny of the cell - undertaking repair activities; entering replicative senescence; inducing cell death; resorting to translesion transactions or altering the metabolism or the expression pattern of the cell. Proper functioning of p53 and its related pathways is essential in multicellular eukaryotes, with failures in the DNA-binding and transactivation properties of p53 usually resulting in cancer. Recent research on some common polymorphic variants of p53 that exhibit differential properties in their ability to induce cell cycle arrest or apoptosis indicate that p53 is not only the 'guardian angel' of the genome, as is commonly believed, keeping its integrity in check and disposing of damaged cells, but it is as well the 'archangel' that is responsible for cutting down the lifespan of the organism by the mechanism of ageing. One function can hardly exist without the other, and it is very individual as to whether carriership of one polymorphic form or another would be beneficial in the particular case, considering the general status of the patient and the specificities of the pathogenesis of the disease or condition in question. Age of the patient seems to be a major determining factor, as the differential pattern in the properties of p53 seems to become more pronounced as age advances. Source

Petkova R.,Scientific Technological Service STS Ltd | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2016

The mechanisms for identification of DNA damage and repair usually manage DNA damage very efficiently. If damaged cells manage to bypass the checkpoints where the integrity of the genome is assessed and the decisions whether to proceed with the cell cycle are made, they may evade the imperative to stop dividing and to die. As a result, cancer may develop. Warding off the potential sequence-altering effects of DNA damage during the life of the individual or the existence span of the species is controlled by a set of larger checkpoints acting on a progressively increasing scale, from systematic removal of damaged cells from the proliferative pool by means of repair of DNA damage/programmed cell death through ageing to, finally, cancer. They serve different purposes and act at different levels of the life cycle, safeguarding the integrity of the genetic backup of the individual, the genetic diversity of the population, and, finally, the survival of the species and of life on Earth. In the light of the theory that cancer is the final checkpoint or the nature's manner to prevent complex organisms from living forever at the expense of genetic stagnation, the eventual failure of modern anti-cancer treatments is only to be expected. Nevertheless, the medicine of today and the near future has enough potential to slow down the progression to terminal cancer so that the life expectancy and the quality of life of cancer-affected individuals may be comparable to those of healthy aged individuals. © 2016 The Author(s). Published by Taylor & Francis. Source

Petkova R.,Scientific Technological Service STS Ltd | Chelenkova P.,Sofia University | Tournev I.,Medical University-Sofia | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2016

Neurons in the adult central nervous system (CNS) are subjected to high levels of oxidative damage that is usually promptly repaired. Transcribed genomic regions are repaired with priority over untranscribed regions. The prioritization of DNA repair in neurons results in modification of the input into the assessment of genomic integrity in order to delay or avoid damage-related apoptosis unless the damage interferes directly with the functioning of the neuron. CNS neurons may be replaced, albeit rarely. Over-stimulation of adult neural progenitor niche caused by accelerated neuronal loss may result in its premature depletion. The combination of the two pathologic mechanisms (increased rates of neuronal death and depletion of the progenitor niche) may eventually result in irreversible loss of specific cell populations in the CNS and/or generalized neuronal loss. Here we propose that the risk of developing sporadic late-onset neurodegenerative disease (LONDD) may be modulated by the individual capacity for detection and repair of DNA damage and the genetic propensity to repair moderate-degree damage or to assess it as irreparable and route the cell towards apoptosis. Thus, subtly deficient DNA damage repair coupled with a tendency to repair the damage rather than kill the damaged cell may be associated with increased risk of cancer, whereas deficient DNA repair coupled with a propensity to destroy damaged cells may increase the risk of LONDD. Extensive studies of individual repair capacity may be needed to test this hypothesis and, potentially, use the results in the assessment of the risk of common late-onset disease. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis. Source

Chelenkova P.,Scientific Technological Service STS Ltd | Petkova R.,Scientific Technological Service STS Ltd | Yochev S.,Bulgarian Ichthyological Society | Vasilev M.,Bulgarian Academy of Science | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2012

Human impact on genetic variability of species is a prominent cause for loss of biodiversity on a global scale. The present work offers evidence that the genetic diversity in Bulgarian native populations of brown trout is already failing because of alteration of the population structure via enhanced human-mediated assortative mating and/or interspecies hybridisation with other salmonids. The risk of adverse genetic consequences to the native populations is already significant. Bulgarian aquaculture may benefit from more strict control policy over stock transfer and release of fish and stock material into the natural water basins. Source

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