025 OXKDATIVE STRESS IN LEUKEMIC PATIENTS A. B. Sarmento Ribeiro, T. Proenca, I. Sousa, A. Teixeira, Pereira, T. Silva, C. Resende de Oliveira Facullty of Medicina, University of Coimbra; Laboratory Neurochemistry and Clinical Hematology, Hospital University of Coimbra;, Hospital Distrital of Figueira Fez.
STRESS AND THE NEUROENDOCRINE-IMMUNE AXIS J. C. Buckingham Department ofNeuroendocrinology, Imperial College School of Medicine, London W6 8RF
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The hypothalamo-pituitary-adrenocortical (HPA) axis provides an essential interface between the internal and external environment, enabling the organism to adapt to noxious stimuli. It is activated by physical (e.g. infection, tissue injury) and emotional stressors and the glucocorticoids (GCs) which are consequently released exert diverse effects which serve collectively to restore homeostasis. Failure to mount an appropriate GC response to stress is potentially hazardous and disturbances in HPA function are now implicated in the aetiology of a variety of diseases. For example, excessive GC secretion causes immunosuppression which may predispose the individual to e.g. infections. Conversely, adrenocortical insufficiency precipitates a vulnerability to stress and is increasingly implicated in the pathogenesis of autoimmune, inflammatory and allergic disorders. In healthy individuals, serum GCs are maintained within narrow limits with elevations occurring only in accord with the circadian rhythm and in conditions of stress. Pivotal to this tight control is a complex servo mechanism through which the GCs negatively regulate their own secretion and thus effectively contain the adrenocortical responses to incoming stimuli (e.g. stress) within appropriate limits. These feedback actions are mediated by multiple molecular mechanisms which include the induction of a protein, lipocortin I (LCl). LCI is particularly effective in quenching the HPA responses to immune insults and also contributes to the powerful anti-inflammatory/immunosuppressive actions of the Gcs.
Reactive oxygen species (ROS) are involved in tumor promotion, while antioxidant defenses may have an anticarcinogenic action. The aim of this study was to evaluate the activity of the antioxidant enzymes glutathione peroxidase (GL-PX) and superoxide dismutase (SOD) in the erythrocytes of 7 leukemia patients (chronic lymphocytic leukemia-LLC) and in 7 healthy volunteers. Reduced glutathione (GSH) and vitamin E/cholesterol (E/CHL) plasma levels were also determined in same population. We also studied the enzymatic defenses in 4 patients with acute lymphoblastic leukemia (LLA) and the production of hydrogen peroxide. The activity of the enzymatic and the defenses determined by a nonenzymatic was spectrophotometric assay and hydrogen production was determined by fluorometric assay. GL-PX and SOD activity was decreased in leukemia patients, GSH and E/CHL plasma levels was higher in LLC patients when compared with controls. These differences had statistical significance (pcO.05). The values that we have found in leukemia patients support the notion that antioxidant mechanisms are deficient and/or free radicals are being generated and possibly contribute to the pathogenesis of leukemia. The levels of GSH found in leukemia patients suggest the involvement of GSH in the resistance of cancer cells to cell death. This work was perfcwmedwith the collaboration of Blood Regional Center of Coimbra and supported by PRODEP and Health Ministety of Portuguese Govemment
This work is generously supported by the Wellcome Trust.
ECOLOGY INDUCED IMMUNE DISORDERS V. A. Chereshnev, B. A. Bachmetyev, N. N. Kevorkov, Ju. I. Shilov, S. V. Shirshev, L. B. Korolevskaya, E. A. Starkova, M. V. Chereshneva, S. P.Tendrikova and M. B. Rayev Department of Immunology, Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Perm, Russia
ALTERATION IN ANTIOXIDANT DEFENCE AS ENDOGENOUS FACTOR OF BREAST CANCER DEVELOPMENT E. Savina, I. Kondakova, E. Slonimskaya Department of Tumor Biochemistq Institute of Oncology, Russian Academy ofMedical Science, Tomsk, Russia Among factors of cancer risk the alteration in antioxidant defence of human organism may play an important role. The purpose of the present study was to estimate antioxidant status in different stages of breast cancer development. We have determined the total antiradical activity, vitamin E and uric acid contents in plasma of 12 healthy donors, 63 patients with precancerous lesions and 18 patients with breast cancer. with a measured activity was antiradical The azo-bisusing 2,2 method chemiluminescence isobutironitrile. Other parameters were determined by means of standard methods. Total antiradical activity level in plasma increased in patients with precancerous lesions (32%) compared with control. Small differences in this parameter were found for patients with breast cancer. Uric acid content decreased in patients with breast precancer (20%) and reached the control level in cancer patients. Vitamin E content increased in patients with precancerous lesions (22,6%) and breast cancer (3 1,5%). Thus, the development of breast cancer is accompanied by significant changes in total antiradical activities and in individual water and lipid-soluble antioxidants of blood plasma. Breast cancer is accompanied by high level of plasma vitamin E and uric acid that provide antiradical activity compared with that of healthy donors.
Considering highly unfavorable ecological situation in West Ural (intensive industrial pollutions and conducting the underground nuclear explosions with the aim of oil extraction), immune system investigation among adult and children living in different environmental regions were conducted. The availability and frequency of immune system disorders revealed in our study were related to age, sex , ecological “pressure” level in different subregions. However, the majority of revealed immune disorders exhibited the phase character and can be subdivided into three consecutive stages: activation, stabilization and inhibition. Regarding definite immune system compartment (T system, B system, phagocytes system) the time of starting and/or the duration of each of these stages were different. Thus, the obtained results suggest that ecology induced immune disorders can be considered as manifestation of human organism adaptive reaction to unfavorable environmental factors.
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