Il: Subburaj Kannan* - [email protected] * Corresponding authorPublished: 07 June 2006 Theoretical Biology and Medical

Il: Subburaj Kannan* – [email protected] * Corresponding authorPublished: 07 June 2006 Theoretical Biology and Medical Modelling 2006, 3:22 doi:10.1186/1742-4682-3-Received: 19 December 2005 Accepted: 07 JuneThis article is available from: http://www.tbiomed.com/content/3/1/22 ?2006 Kannan; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Procyanidin B1 web Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractBackground: Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood. Hypothesis: A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo. Conclusion: The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity.Background: review of the literatureMulti-drug resistance: a multi-step process After exposure to chemotherapeutic drugs, lymphoid cells develop along two distinct pathways. First, a cell population susceptible to the drugs dies by apoptosis or necrosis, depending on the severity of treatment. Secondly, a few cells evolve one or more mechanisms for survival, resisting the damage inflicted by the drugs. It is well known that chemotherapeutic drugs induce tumor cell death via apoptosis through DNA damage, and, in particular, activation of proteolytic enzymes involved in programmed cell death. When one drug fails, various others are tried as parts of a therapeutic regimen. Such drugs kill cancer cells by increasing their sensitivity via alterations in internal mechanisms, a desired outcome for effective chemotherapy. Some tumor cells evolve mechanisms, as yet poorlyunderstood, by which they acquire resistance to structurally and functionally unrelated drugs; this is referred to as multi-drug resistance.Multi-drug resistance: a selective adaptation mechanism Distinct factors contributing to the formation of tumorigenic phenotypes ensure that each malignant cell is unique in terms of activation of oncogenes and inactivation of tumor suppressor genes. Drug-exposed tumor cells are subjected to sustained to oxidative stress and become tolerant to it. During this time window, selection pressure imposed by the chemotherapeutic drugs causes the selective overgrowth of cells that can withstand them. It is also possible that normal, but susceptible, cells may acquire drug resistance by cellular overgrowth in their neighborhood [1].Page 1 of(page number not for citation purposes)Theoretical Biology and Medical Modelling 2006, 3:http://www.tbiomed.com/content/3/1/Multi-drug resistance: an intrinsic or acquired phenomenon Development of drug resistance could be either intrinsic or acquired during neop.