Enhancement of radiation induced cell death in chicken B lymphocytes by withaferin A.

Withaferin A (WA), a plant withanolide, has shown significant radiosensitizing effect in vitro and in vivo. Inhibition of DNA repair has been suggested as a mechanism of radiosensitization by WA. To test this, the effect of withaferin A on survival of DT40 chicken B-lymphocyte cell line and its repair deficient single gene mutants Rad54-/-, Ku70-/- and double mutant Ku70-/- /Rad54-/- after irradiation was studied. Exponentially growing cells were treated for 1 hr with 5 microM WA and then exposed to different doses of X-rays. Cell survival was studied by clonogenic assay. WA significantly reduced survival of DT40, Ku70-/- and Ku70-/- /Rad54-/-, but not Rad54-/- cells, suggesting that WA enhances radiosensitivity by interfering with homologous repair, the major pathway of DSB repair in these cells. Inhibition of DNA repair is further indicated in a significant decrease in surviving fraction of DT40 cells by post-irradiation incubation with WA. This could have relevance to cancer radiotherapy.

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.

Hyperthermia in cancer research: current status.

There are critical maximum temperatures above which irreversible damage occurs in cells and tissues. Exposure to high temperature, referred to as hyperthermia (HT), can result in cell death, tissue damage or even death of the organism. Clinical application of HT as a primary treatment or as an adjuvant to radio-/chemo- therapy of cancer is based on its ability to cause localized tumor tissue damage. Experimental data provide HT with a strong biological rationale. Early clinical experience suggested that HT will become an important modality as an adjuvant to radiotherapy in the treatment of human malignancies, but its application is currently limited to mainly superficial tumors. Its full realization as a treatment modality for cancer therapy awaits further laboratory investigations as well as controlled clinical trials. A better understanding of the biological mechanisms of its action, interaction with chemotherapeutic drugs and radiation damage, role of tumor microenvironment such as oxygen status and pH of tumors, and kinetics of thermotolerance can lead to refinement in its clinical implementation. The present review attempts to analyse the published literature during the last one and half decades.