Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

<p>Abstract</p> <p>Background</p> <p>Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB), chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results has reduced general application. An additional type of information is required for the increasing application of high-LET radiation in cancer therapy: the Relative Biological Effectiveness (RBE) for effects in tumours and normal tissues. Relevant information on RBE values might be derived from studies on cells in culture.</p> <p>Methods</p> <p>To evaluate relationships between DNA-DSB, chromosome aberrations and the clinically most relevant effect of cell reproductive death, for ionizing radiations of different LET, dose-effect relationships were determined for the induction of these effects in cultured SW-1573 cells irradiated with gamma-rays from a Cs-137 source or with α-particles from an Am-241 source. RBE values were derived for these effects. Ionizing radiation induced foci (IRIF) of DNA repair related proteins, indicative of DSB, were assessed by counting gamma-H2AX foci. Chromosome aberration frequencies were determined by scoring fragments and translocations using premature chromosome condensation. Cell survival was measured by colony formation assay. Analysis of dose-effect relations was based on the linear-quadratic model.</p> <p>Results</p> <p>Our results show that, although both investigated radiation types induce similar numbers of IRIF per absorbed dose, only a small fraction of the DSB induced by the low-LET gamma-rays result in chromosome rearrangements and cell reproductive death, while this fraction is considerably enhanced for the high-LET alpha-radiation. Calculated RBE values derived for the linear components of dose-effect relations for gamma-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0 ± 0.3, 14.7 ± 5.1, 15.3 ± 5.9 and 13.3 ± 6.0 respectively.</p> <p>Conclusions</p> <p>These results indicate that RBE values for IRIF (DNA-DSB) induction provide little valid information on other biologically-relevant end points in cells exposed to high-LET radiations. Furthermore, the RBE values for the induction of the two types of chromosome aberrations are similar to those established for cell reproductive death. This suggests that assays of these aberrations might yield relevant information on the biological effectiveness in high-LET radiotherapy.</p

New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP)