RESUMEN
The objective of this study was to compare the biokinetics of injected H-labeled light (HTO) and heavy (DTO) water in CBA/CaJ mice and to compare the organ distribution and/or body content of H administered by chronic ingestion for 1 mo to C57Bl/6J mice, as either H-labeled water or H-labeled amino acids (glycine, alanine and proline). HTO and DTO were administered to CBA/CaJ mice by single intraperitoneal injection and body retention was determined for up to 384 h post-injection. Tritium-labeled water or H-labeled amino acids were given to C57Bl/6J mice ad libitum for 30 d in drinking water. Body content and organ distribution of H during the period of administration and subsequent to administration was determined by liquid scintillation counting. No differences were found between the biokinetics of HTO and DTO, indicating that data generated using HTO can be used to help assess the consequences of H releases from heavy water reactors. The results for H-water showed that the concentration of radionuclide in the mice reached a peak after about 10 d and dropped rapidly after the cessation of H administration. The maximum concentration reached was only 50% of that in the water consumed, indicating that mice receive a significant fraction of their water from respiration. Contrary to the findings of others, the pattern of H retention following the administration of a cocktail of the labeled amino acids was very little different from that found for the water. This is consistent with the suggestion that most of the ingested amino acids were rapidly metabolized, releasing water and carbon dioxide.
Asunto(s)
Aminoácidos/farmacocinética , Óxido de Deuterio/farmacocinética , Deuterio/farmacocinética , Agua Potable/metabolismo , Marcaje Isotópico/métodos , Tritio/farmacocinética , Administración Oral , Aminoácidos/administración & dosificación , Aminoácidos/química , Animales , Deuterio/administración & dosificación , Deuterio/química , Óxido de Deuterio/administración & dosificación , Óxido de Deuterio/química , Femenino , Inyecciones Intravenosas , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos CBA , Especificidad de Órganos/fisiología , Distribución Tisular , Tritio/administración & dosificación , Tritio/químicaRESUMEN
In this study, we sought to determine whether low-dose ionizing radiation, previously shown to induce a systemic adaptive response in C57BL/6J mice, is capable of enhancing the rate of DNA double-strand break repair. Repair capacity was determined by measuring γ-H2AX levels in splenic and thymic lymphocytes, using flow cytometry, at different times after a challenge irradiation (2 Gy, (60)Co). Irradiation with low doses (20 and 100 mGy) was conducted in vivo, whereas the challenge dose was applied to primary cultures of splenocytes and thymocytes in vitro 24 h later. Obtained kinetics curves of formation and loss of γ-H2AX indicated that cells from low-dose irradiated mice did not express more efficient DNA double-strand break repair compared to controls. Immunoblot analysis of γ-H2AX and Phospho-Ser-1981 ATM confirmed that DNA damage signaling was not modulated by preliminary low-dose radiation. Mouse embryonic fibroblasts of C57BL genetic background failed to show clonogenic survival radioadaptive response or enhanced repair of DNA double-strand breaks as evaluated by immunofluorescence microscopy of γ-H2AX foci. Our results indicate that radiation adaptive responses at systemic levels, such as increases in the tumor latency times in aging mice, may not be mediated by modulated DNA repair, and that the genetic background may affect expression of a radioadaptive response.