Hamid Vaghef

Sensitivity of human pancreatic islets to peroxynitrite-induced cell dysfunction and death.

Nitric oxide and peroxynitrite (generated by the reaction of nitric oxide with the superoxide anion) may both be mediators of β‐cell damage in early insulin‐dependent diabetes mellitus. We observed that acute exposure of primary cultured human pancreatic islets to peroxynitrite results in a significant decrease in glucose oxidation and islet retrieval. DNA strand breaks in single human and rat islet cells are detectable after acute peroxynitrite exposure, followed by a decrease in islet cell survival after 1 h and 24 h. Cell death appeared to occur via a toxic cell death mechanism (necrosis) rather than apoptosis, as suggested by vital staining and ultrastructural evidence of early membrane and organelle degradation, mitochondrial swelling and loss of matrix. This study demonstrates for the first time that cultured human pancreatic islets are susceptible to the noxious effects of peroxynitrite.

Evaluation of radiation-induced DNA damage and DNA repair in human lung cancer cell lines with different radiosensitivity using alkaline and neutral single cell gel electrophoresis

Using the comet assay, radiation-induced DNA strand breaks were evaluated in human lung cancer cell lines with different radiosensitivity (U-1285, U-1906E, U-1752 and U-1810). Single strand breaks were more sensitive indicators of the radiation-induced damage than double strand breaks. However, there was no consistent pattern in the way the various cell lines responded to 1-5 Gy of gamma-irradiation and all cell lines showed a remarkably efficient DNA repair after 1 h. In a separate study of the repair kinetics of DNA double strand breaks, the radioresistant cell line U-1810 showed a more efficient initial strand rejoining than the radiosensitive cell line U-1285 after irradiation at 2 Gy. The latter finding suggests that the detection of early DNA repair may be useful when monitoring the intrinsic radiosensitivity of human lung cancer cells.