ABSTRACT
The current review summarizes the results of investigations on the phenomenon of the decrease of cell radiosensitivity after the impact of various damaging factors in small doses. This phenomenon is known as an adaptive response (AR). It has been described in a number of biological objects, but the author has reviewed only the researches that have been done on human peripheral blood lymphocytes. Lymphocyte AR is specifically characterized by the fact that the entire cascade of events that decrease radiosensitivity occurs during one mitotic cycle. This feature distinguishes lymphocyte AR from the phenomenon of cell adaptation to chronic small dose irradiation. In this review, the author pays special attention to research on the initial stages of the AR formation. The author presumes that the AR occurs as a result of nonspecific intracellular changes that are a signal of the disruption in cell homeostasis. Several researchers define the state that results from this as the state of stress. After a cell transfers to this state there is a launch of biochemical processes that are able to protect the cell in case of future exposure to large doses of damaging factors (including irradiation). These processes are not determined strictly by the initial stimulus and are not initiated directly by the impact of the external factor that induced the AR. The particular method of decreasing radiosensitivity has not been determined and its selection depends on cell genotype, conditions of the experiment, etc. This might be the synthesis of various types of reparation enzymes, the synthesis of antioxidant enzymes, the activation of cell division or apoptosis. Cells that do not turn into the stress state do not form an AR. If there is no damaging shock-like impact after the cell enters the stress, the cell gets back to the normal rest state and the ability to form an AR disappears.
Subject(s)
Adaptation, Physiological/genetics , DNA Repair , Leukocytes, Mononuclear/radiation effects , Radiation Tolerance/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , DNA Damage , Gene Expression Regulation , Genotype , Homeostasis , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Mitosis , Radiation, Ionizing , Signal Transduction , Stress, PhysiologicalABSTRACT
The oxidative status (ROS), markers activation expression (CD69), proliferation activity (Ki67), proapoptotic antigen (CD95) have been investigated on healthy donors and patients with prostatic gland cancer in human blood lymphocytes. The lymphocyte reaction in vitro on γ-irradiation at different doses (0.05-1.0 Gy) has been determined too. It was shown that in these two types of individuals the ROS content does not differ and the reaction on irradiation is not different either. Essential is the difference between the marker expression in lymphocytes of healthy donors and patients with tumour: in individuals with cancer the content of lymphocytes with CD69+ phenotype (in non active situation) and CD95+ increases, the expression of marker Ki67 decreases. The lymphocyte response to irradiation in healthy and tumour lymphocytes is distinguished. Irradiation at doses 0.05-10.0 Gy on tumour patients lymphocytes markers does not influence expression. In healthy donors' lymphocytes the expression of markers is changed considerably, the reaction depends on the marker type: expression of CD69 marker decreases (tendency); expression of Ki67 decreases too; it is unusual that the expression of CD95 changes--it decreases after irradiation at the doses of 0.05-1.0 Gy, then increases with dose. So this work shows the changes in tumour patients' blood lymphocytes in comparison with healthy donors' lymphocytes. The possible mechanisms of the observed phenomenon are discussed.
Subject(s)
Ki-67 Antigen/biosynthesis , Lymphocytes/radiation effects , Prostatic Neoplasms/genetics , fas Receptor/biosynthesis , Apoptosis/radiation effects , Cell Proliferation/radiation effects , Dose-Response Relationship, Radiation , Gamma Rays , Gene Expression Regulation, Neoplastic/radiation effects , Healthy Volunteers , Humans , Lymphocytes/pathology , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Radiation Tolerance , Reactive Oxygen Species/radiation effectsABSTRACT
Study of the mutagenic action of methyl nitrosourea (MNU) on the CHO-AT3-2 Chinese hamster cell at 2 regimes of cell treatment (a short-term regime and prolonged 1-h treatment) revealed that increase in the duration of treatment enhanced both cell lethality and clastogenic and mutagenic effects at the TK locus and did not influence the mutation frequency at the OUAr locus. On the basis of kinetic considerations it can be concluded that the base-pair substitution-type mutants (e.g., OUAr) appear as a result of DNA alkylation and the mutants at loci with a wide spectrum of registered mutants (the TK locus) are related to a greater extent to the carbamoylating activity of MNU. This conclusion is confirmed by measurements of the effects of sequential treatment with MNU (7 min) and KNCO (1 h). A synergistic increase in lethality, clastogenicity and mutagenicity at the TK locus was found in experiments with the combined treatment of cells with ethyl methanesulfonate (EMS) and KNCO. Besides, pretreatment of cells with potassium cyanate and subsequent exposure to MNU, EMS and benzopyrene (BP) produced synergistic effects in all the tests: lethality, clastogenicity and mutation frequency at the OUAr and TK loci. Posttreatment of cells with KNCO also led to a synergistic increase in the effects of MNU, EMS and BP treatment in several tests, but not in the OUAr locus. The possible mechanism and levels of interactions between alkylation and carbamoylation and the possibility that potassium cyanate causes supramolecular lesions are discussed.
