title: [Ways of realizing apoptosis of human lymphocytes induced by UV-light and reactive oxygen species].
abstract: Changes of DNA structural condition, the level of membrane Fas-receptor expression, caspase-3 functional activity, concentrations of Ca2+, p53 and cytochrome c proteins of human lymphocytes in dynamics of apoptosis development induced by UV-light (240-390 nm) at doses 151, 1510, 3020 J/m2 and reactive oxygen species (superoxide anion-radical, hydroxyl radicals, hydrogen peroxide, singlet oxygen) have been studied. UV-light and reactive oxygen species have been established to induce fragmentation of lymphocyte DNA after 20 h incubation of the modified cells. It has been shown, that the increase in the expression level of membrane death Fas-receptors is observed during 1-5 h after exposure oflymphocytes to UV-light and ROS compared with intact cells. Also revealed is augmentation of lymphocyte caspase-3 functional activity 4 h after generation of singlet oxygen, hydroxyl radical and hydrogen peroxide addition, as well as 8 and 24 and 6 and 8 h after UV-irradiation of the cells at doses 151 and 1510 J/m2, correspondingly. Using DNA-comet method made it possible to tape that DNA damages (single-strand breaks) appear 15-20 min after lymphocyte UV-irradiation at doses 1510 and 3020 J/m and addition of hydrogen peroxide in concentration 10(-6) mol/l (C1 type comet) and reach their maximum 6 h after modification of the cells (C2 and C3 type comets). It has been observed, that 6 h after exposure oflymphocytes to hydrogen peroxide and UV-light at doses 1510 and 3020 J/m2, the p53 level of investigated cells raises. It has also been shown that the higher level of calcium in lymphocyte cytosol in conditions of UV-light exposure (1510 J/m2) and exogenous generation of reactive oxygen species is caused by Ca2+ exit from intracellular depots as a result of activating the components of the phosphoinositide mechanism for transferring information into a cell. Ideas about correlation between alterations of the calcium level and initiation of programmed cellular destruction of human lymphocytes after exposure to UV-irradiation and ROS is proposed. The authors come to the conclusion about the leading role of receptor-mediated (Fas-dependent) caspase- and p53-dependent ways of realizing apoptosis oflymphocytes induced by UV-light at doses 151 and 1510 J/m2 and active oxygen metabolites. The pattern of the possible intracellular events leading to apoptotic destruction of lymphocytes after their UV-irradiation is offered.
authors.forename: V G
authors.initials: VG
authors.lastname: Artiukhov
authors.forename: M S
authors.initials: MS
authors.lastname: Trubitsyna
authors.forename: M A
authors.initials: MA
authors.lastname: Nakvasina
authors.forename: E V
authors.initials: EV
authors.lastname: Solov'eva
authors.forename: O V
authors.initials: OV
authors.lastname: Lidokhova
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002118:Calcium / Q000032:analysis; D053148:Caspase 3 / Q000528:radiation effects; D002478:Cells, Cultured; D020552:Comet Assay / Q000379:methods; D053938:DNA Fragmentation / Q000528:radiation effects; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000378:metabolism / Q000528:radiation effects
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D053148:Caspase 3; D002118:Calcium