Showing papers by "Badri N. Pandey published in 2007"

Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line.

Abstract: The development of radio-resistant tumor cells might be overcome by the use of tumor selective cytotoxic agents in combination with radiation treatment of cancer. Thus, we are exploring the radiomodifying potential of D7, a tumor-inhibitory compound derived from a plant product, diospyrin, in breast carcinoma cells, MCF-7. The present study indicated that D7 could enhance the radiation-induced cytotoxicity and apoptosis through down-regulation of the anti-apoptotic Bcl-2 and COX-2 gene expression, and up-regulation of pro-apoptotic genes, like p53 and p21. The higher expression of PUMA, a pro-apoptotic protein was also observed in the combination treatment. Effect of D7 on up-regulation of p21 expression in irradiated MCF-7 cells was concomitant with the cell cycle arrest in the G1 phase. Thus, it was concluded that D7 could sensitize the effect of radiation in breast carcinoma by regulating the gene expression involved in cell cycle and apoptosis.

Acute exposure of uranyl nitrate causes lipid peroxidation and histopathological damage in brain and bone of Wistar rat.

Abstract: Although the kidneys are the main target organs for uranium (U) toxicity, recent studies have shown that U can cross the blood-brain barrier to accumulate in the brain. Uranyl nitrate (U-238)induced oxidative damage was investigated in brain and bone of Wistar rats after intraperitoneal injection of uranyl nitrate at acute doses either nephrotoxic (576 microg of U/kg body weight) or subnephrotoxic (144 microg U/kg body weight). The health effects of U administration at 576 microg of U/kg body weight were seen in terms of decrease in food intake and no gain in body weight compared to respective controls. These alterations were correlated with increased lipid peroxidation as measured by thiobarbituric acid reactive substances in rat brain and bone. However, at lower dosage of U (144 microg U/kg body weight), no significant lipid peroxidation was observed in brain and bone. Histological examination of U-treated (576 microg of U/kg body weight) rat brain tissues showed marked and diffuse cystic degeneration and a similar pattern in histological alterations was observed in kidneys in treated animals; whereas no significant histological change was observed in rat brains and kidney treated with a lower dose of U (144 microg U/kg body weight). It is concluded that administration of U at an acute nephrotoxic dose caused oxidative stress in brain and bone manifested as lipid peroxidation and histopathological damage.

Radiation-induced incidence of thymic lymphoma in mice and its prevention by antioxidants

Abstract: Previous reports from our laboratory have shown that in Swiss female mice exposed to an acute dose (3 Gy) of whole body irradiation (WBI), induced thymic lymphoma (TL) resulted after three to four weeks of exposure. The present study was aimed to further evaluate dependency on gender and effect of age of mice at the time of irradiation on TL incidence. A significant decrease in body weight gain was observed in female mice exposed to WBI, which was found to be correlated with the increase in weight and size of thymus, compared to their respective controls. An increase in TL incidence was observed with the increased postirradiation time, which was 47, 80, and 93% after 90, 120, and 150 days of WBI, respectively, in female mice. In irradiated female mice, the TL incidence was significantly higher and the growth of tumor in terms of weight and size was more aggressive than in males of the same age. Moreover, mice with higher age groups at the time of irradiation showed substantial decrease in TL incidence and its aggressiveness; and these effects were more conspicuous in males than in females. In mice irradiated at the age group of three to four weeks, the TL incidence was 83 and 72% in female and male, respectively, which was decreased to 74% in female and 14% in male in the age group of 12-13 weeks. It was further observed that the postirradiation feeding of animals with antioxidants resulted in a significant decrease in TL incidence, and the prevention in TL incidence was more in animals fed with curcumin (55%) than with ascorbic acid and eugenol (20%). These results have provided significant new findings on the phenomenon of radiation-induced TL incidence related to gender and age at the time of irradiation and its prevention by postirradiation antioxidant feeding to mice.

Mechanisms underlying the expression and propagation of low dose/low fluence ionising radiation effects

Abstract: Health risks to human and non-human biota exposed to low dose ionising radiation remain ambiguous. The need to establish risk assessment standards based on the mechanisms underlying low level radiation exposure has been recognised by regulatory agencies as critical to adequately protect people and to make the most effective use of national resources. Both gap-junction intercellular communication and oxidative metabolism have been shown to mediate 'adaptive' and 'bystander' effects in mammalian cells exposed in vitro to low dose/low fluence ionising radiation. While adaptive responses are thought to mitigate the harmful effects of radiation, bystander effects have been suggested to amplify its consequences. The exact molecular steps by which adaptive and bystander effects are elicited have not been defined. Here we discuss a few of the molecular and biochemical events underlying these effects. Our data indicate that dose, dose-rate, and the linear energy transfer of the radiation are critical in inducing the changes that determine whether protective or harmful effects are expressed at low dose/low fluence ionising radiation.