A. Biete

OXIDATIVE DAMAGE OF MITOCHONDRIAL AND NUCLEAR DNA INDUCED BY IONIZING RADIATION IN HUMAN HEPATOBLASTOMA CELLS

PURPOSE Since reactive oxygen species (ROS) act as mediators of radiation-induced cellular damage, the aim of our studies was to determine the effects of ionizing radiation on the regulation of hepatocellular reduced glutathione (GSH), survival and integrity of nuclear and mitochondrial DNA (mtDNA) in human hepatoblastoma cells (Hep G2) depleted of GSH prior to radiation. METHODS AND MATERIALS GSH, oxidized glutathione (GSSG), and generation of ROS were determined in irradiated (50-500 cGy) Hep G2 cells. Clonogenic survival, nuclear DNA fragmentation, and integrity of mtDNA were assessed in cells depleted of GSH prior to radiation. RESULTS Radiation of Hep G2 cells (50-400 cGy) resulted in a dose-dependent generation of ROS, an effect accompanied by a decrease of reduced GSH, ranging from a 15% decrease for 50 cGy to a 25% decrease for 400 cGy and decreased GSH/GSSG from a ratio of 17 to a ratio of 7 for controls and from 16 to 6 for diethyl maleate (DEM)-treated cells. Depletion of GSH prior to radiation accentuated the increase of ROS by 40-50%. The depletion of GSH by radiation was apparent in different subcellular sites, being particularly significant in mitochondria. Furthermore, depletion of nuclear GSH to 50-60% of initial values prior to irradiation (400 cGy) resulted in DNA fragmentation and apoptosis. Consequently, the survival of Hep G2 to radiation was reduced from 25% of cells not depleted of GSH to 10% of GSH-depleted cells. Fitting the survival rate of cells as a function of GSH using a theoretical model confirmed cellular GSH as a key factor in determining intrinsic sensitivity of Hep G2 cells to radiation. mtDNA displayed an increased susceptibility to the radiation-induced loss of integrity compared to nuclear DNA, an effect that was potentiated by GSH depletion in mitochondria (10-15% intact mtDNA in GSH-depleted cells vs. 25-30% of repleted cells). CONCLUSION GSH plays a critical protective role in maintaining nuclear and mtDNA functional integrity, determining the intrinsic radiosensitivity of Hep G2. Although the DNA repair is a complex process that is not yet completely understood, the protective role of GSH probably does not seem to involve the repair of classical DNA damage but may relate to modification of DNA damage dependent signaling.

Prospective evaluation of squamous cell carcinoma and carcinoembryonic antigen as prognostic factors in patients with cervical cancer.

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value.

Anti-inflammatory effects of low-dose radiotherapy: Indications, dose and radiobiological mechanisms involved

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.ZusammenfassungNiedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.

Anti-inflammatory effects of low-dose radiotherapy

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.ZusammenfassungNiedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.

Synchrotron radiation in cancer treatments and diagnostics:: an overview

During the last 30 years many groups have carried out experiments and trials to develop new imaging and radiotherapy techniques in oncology, based on the use of synchrotron X-rays. There are several synchrotron biomedical stations around the world, which offer an excellent platform to improve either the imaging diagnosis or radiotherapy treatment for different tumour types. In the coming months the first radiotherapy clinical trials will be seen at the Biomedical Beamline at the ESRF synchrotron in Grenoble (France). In this article we highlight the results of some of the techniques and strategies that have been developed at different biomedical synchrotron stations.

Anti-inflammatory effects of low-dose radiotherapy@@@Entzündungshemmende Effekte von niedrigdosierter Strahlentherapie: Indications, dose, and radiobiological mechanisms involved@@@Indikationen, Dosis und zugrundeliegende radiobiologische Mechanismen

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.ZusammenfassungNiedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.