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Aims: Chromium (III) is an insulinomimetic agent whose biological and/or environmental availability is frequently in the form of Cr(VI), which is known to be toxic. Wall-less mutant of Neurospora crassa (FGSC stock no. 4761) is known to possess insulin receptor in its cell membrane and hence is a good model for Cr toxicity studies. This study explores the toxicity of Cr(VI) and the possible consequences on simultaneous exposure to insulin in N. crassa. Methods and Results: Comet assay of N. crassa cells treated with 100 μmol l−1 Cr(VI) showed up to 50% reduction in comet tail lengths when incubated simultaneously with 0·4 U insulin. Fluorescence measurement in Cr(VI)-treated cells using DCFH-DA showed six- to eightfold increase in free radical generation, which was reduced to fourfold by 0·4 U insulin. Annexin-V/PI Flow cytometry analysis indicated necrotic cell death up to 28·7 ± 3·6% and 68·6 ± 2·5% on Cr(VI) exposure at concentrations 100 and 500 μmol l−1 which was reduced by 68·3 ± 3·2% and 48·9 ± 3·6%, respectively, upon addition of insulin. Conclusion: Insulin-mediated protection from DNA damage by Cr(VI) is because of scavenging of free radicals liberated during exposure to Cr(VI). Significance and Impact of the Study: Overall, Cr(VI) toxicity depends upon available insulin, indicating that Cr(VI) toxicity may be a serious issue in insulin-deficient individuals with diabetes.

We investigated the effect of UV-B irradiation on PI 3-kinase activity in human fetal hepatocytes. When cells were exposed to monochromatic (304nm) UV-B light, a significant increase in intracellular PI 3-kinase activity was observed in a dose dependent manner with maximal activity upon 1500 Jm(-2) irradiation. At 1500 Jm(-2) dose PI 3-kinse activity increased by 80% in membrane fraction of fetal hepatocytes of 25 weeks gestation. PI 3-kinse inhibitors wortmannin and LY294002 specifically inhibited the UV-B induced lipid kinase activity and blocked significantly the UV-B induced cell viability. The data suggests a correlation between cell survival and elevated levels of PI 3-kinase and suggest that UV-B irradiation at a dose of 1500 Jm(-2) is ideal for fetal hepatocyte transplantation. Also, PI 3-kinase levels could be a representative marker for viable UV-B irradiated fetal hepatocytes for transplantation.