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101.
The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. 相似文献
102.
Irradiation with UV-A of normal human fibroblasts in phosphate-buffered saline induced cell death, measured as lack of colony-forming ability. A specially filtered sunlamp, emitting wavelengths greater than 330 nm, was used as UV-A source. After UV-A irradiation, single-strand breaks (alkali-labile bonds) could be detected in DNA; these lesions were rapidly repaired. The induction of these single-strand breaks was almost eliminated when irradiation was performed in the presence of catalase. However, catalase, when present during UV-A irradiation, did not reduce cell death of the fibroblasts. Excision repair, monitored as unscheduled DNA synthesis, was induced strongly by irradiation with UV-C (predominantly 254 nm), but could not be detected after UV-A irradiation. Moreover, very little accumulation of incision breaks during post-irradiation incubation with hydroxyurea and 1-beta-D-arabinofuranosylcytosine (araC) was detected after UV-A. This is consistent with the low amount of pyrimidine dimers (measured as UV-endonuclease susceptible sites) induced by UV-A. Xeroderma pigmentosum fibroblasts of complementation group A, which are extremely sensitive to UV-C irradiation, showed the same sensitivity to UV-A as normal fibroblasts. The results indicate that lethality by UV-A wavelengths greater than 330 nm is caused by lesions other than single-strand breaks (alkali-labile bonds) and pyrimidine dimers. 相似文献
103.
MKP-1 Is Necessary for T Cell Activation and Function 总被引:1,自引:0,他引:1
Yongliang Zhang Joseph M. Reynolds Seon Hee Chang Natalia Martin-Orozco Yeonseok Chung Roza I. Nurieva Chen Dong 《The Journal of biological chemistry》2009,284(45):30815-30824
MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs) that negatively regulate MAPK activities have recently emerged as critical players in both innate and adaptive immune responses. MKP-1, also known as DUSP1, was previously shown to negatively regulate innate immunity by inhibiting pro-inflammatory cytokine production. Here, we found that MKP-1 is necessary in T cell activation and function. MKP-1 deficiency in T cells impaired the activation, proliferation, and function of T cells in vitro, associated with enhanced activation of JNK and reduced NFATc1 translocation into the nucleus. Consistently, MKP-1−/− mice were defective in anti-influenza immunity in vivo and resistant to experimental autoimmune encephalomyelitis. Our results thus demonstrate that MKP-1 is a critical positive regulator of T cell activation and function and may be targeted in treatment of autoimmune diseases. 相似文献
104.
Intramuscular administration of testosterone (T) to male orfemale rats produced a significant increase in the rate of developmentof the intermediate type of taste bud cells. T treatment produceda similar effect in rats previously submitted to the in-blockor selective removal of the main salivary glands. 5-Hydroxytryptamine(5-HT) and noradrenaline (NA) concentrations in the vallatepapilla of normal rats were sensitive to T. The concentrationof 5-HT decreased significantly and the concentration of NAincreased slightly, both with respect to the controls. 相似文献