ABSTRACT
In the present studies, the role of oxidative stress in radiosensitization by a combination of 2-DG and 6-aminonicotinamide (6-AN) was examined in a human glioma cell line (BMG-1: wild type p53). Presence of 2-DG or 6-AN for 4 hr after irradiation (gamma ray 2.5 Gy) significantly enhanced the radiation-induced cell death by 18% and the combination (2-DG + 6-AN) enhanced the cell death by 35%. Neither 2-DG nor 6-AN had any further significant effect on the glutathione levels in irradiated cells. However, the combination (2-DG + 6-AN) caused a significant decrease in GSH content, increase in GSSG levels, and enhanced the superoxide radical generation under these conditions. The enhanced cell death caused by the combination (2-DG + 6-AN) mainly resulted by the process of apoptosis as revealed by annexin V binding and was associated with elevated levels of Cyclin B1. However, no significant change was observed in the levels of Bcl-2. Thus, for the first time, our results have demonstrated that the radiosensitizing effects of these modifiers could also be mediated through alterations in the oxidative stress besides energy limited inhibition of repair and recovery processes.
Subject(s)
6-Aminonicotinamide/administration & dosage , Cell Line, Tumor , Deoxyglucose/administration & dosage , Humans , Oxidative Stress , Radiation-Sensitizing Agents/administration & dosageABSTRACT
La radioquimioterapia concomitante aparece en los últimos años como una alternativa en el manejo de los pacientes portadores de cáncer avanzados de cabeza y cuello. En el Servicio de Otorrinolaringología del Hospital Carlos Van Buren planificamos un protocolo de estudio en pacientes portadores de cáncer escamocelular avanzados de cabeza y cuello, consistente en radioquimioterapia concomitante, 2 Gy diarios por 5 días semanales, completando 6600 a 7000 rad. asociado a cisplatino en dosis de 100 mgr/m² cada 21 días por 3 veces (los días 1,22 y 43). 30 pacientes se incluyeron en el estudio. 28 fueron analizados: 25 hombres y 3 mujeres. La edad promedio fue de 64 años. 8 casos correspondían al estadio III y 20 a estadio IV. 12 casos de localización en hipofaringe, 8 en laringe, 4 en orofaringe, 3 en cavidad oral y 1 en pirámide nasal. Se observó respuesta completa en 18 pacientes (64 por cientos), respuesta parcial en 9 pacientes (32 por ciento) y no respuesta en 1 paciente (4 por ciento). La sobrevida general fue de un 64,3 por ciento. La toxicidad renal y hematológica fueron los efectos adversos más comunes
Subject(s)
Humans , Male , Adolescent , Adult , Female , Middle Aged , Neoplasms, Squamous Cell , Head and Neck Neoplasms , Cisplatin , Neoplasms, Squamous Cell , Disease-Free Survival , Head and Neck Neoplasms , Neoplasm Staging , Radiation-Sensitizing Agents/administration & dosageABSTRACT
Effect of chlorpromazine with biological metal ions, viz. calcium, magnesium, zink and copper was studied on T. ferrooxidans cell system. Chlorpromazine, calcium and magnesium alone could produce radioprotection. Maximum radioprotection was exhibited by chlorpromazine at lower concentration while copper and zink offered radiosensitization. However, combination of chlorpromazine with all biological metal ions exhibited radiosensitization. Dose modifying factor by chlorpromazine at lower concentration (0.025 mM) was 0.754 while in combination with Ca2+, Mg2+, Cu2+ and Zn2+ was 1.08, 1.25, 1.37 and 1.389 respectively. The possible interaction between chlorpromazine and biological metal ions is discussed at cellular membrane level.