The effect of vitamin E on cytotoxicity induced by Na2CrO4 was evaluated by colony-forming assay using Chinese hamster V-79 cells. Pre-treatment with alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure to Na2CrO4 resulted in a marked decrease in the cytotoxicity caused by this compound. The reduction of chromate-induced cytotoxicity was observed at all concentrations of Na2CrO4 (5-15 microM), and the protective effect increased with higher concentrations of vitamin E (5-25 microM). The level of glutathione reductase activity, which is capable of reducing chromate, was not affected by cellular pre-treatment with vitamin E. However, Na2CrO4 decreased glutathione reductase activity in a concentration-dependent fashion (5-15 microM) and pretreatment with vitamin E resulted in a significant recovery of enzyme activity suppressed by Na2CrO4, suggesting that this enzyme inhibition is linked to the cytotoxicity of this metal. Electron spin resonance studies showed that a paramagnetic chromium (V) complex was formed in cells treated with Na2CrO4, and that cellular pre-treatment with vitamin E reduced the formation of this chromium (V) intermediate. These results indicate that vitamin E protects cells from chromate-induced cytotoxicity as well as from enzyme inhibition, and also suggest that Na2CrO4-induced cytotoxicity is mediated by the generation of a reactive intermediate.

We treated genetically mast cell-deficient WCB6F1 Sl/Sld mice and the congenic normal (WCB6F,-+/+) mice with the c-kit ligand recombinant rat stem cell factor" (rrSCF'"; 100 ,ug/kg per d, subcutaneously) or with vehicle for 21 d, then passively sensitized the mice with anti-dinitrophenol3 40 immunoglobulin E (IgE) antibodies, and 1 d later measured the changes in heart rate, pulmonary dynamic compliance, and pulmonary conductance, and assessed the death rates associated with intravenous challenge of these animals with specific antigen. rrSCF 4 treatment induced the development of mast cells in SI/Sid mice, and these mice exhibited tachycardia, but not death, after challenge with IgE and antigen. rrSCF'" treatment induced mast cell hyperplasia in + /+ mice, but the cardiopulmonary changes associated with passive anaphylaxis in these mice were virtually indistinguishable from those observed in control +/+ mice treated with vehicle instead of rrSCF'".Moreover, the highest dose of antigen challenge produced significantly fewer fatalities in rrSCF'`-treated than in vehicletreated +/+ mice (1/11 vs. 8/11, respectively, P < 0.01).Thus, in normal mice, chronic treatment with rrSCF " induces mast cell hyperplasia but does not increase, and in certain respects diminishes, the severity of IgE-dependent anaphylactic reactions. (J. Clin. Invest. 1993Invest. . 92:1639Invest. -1649

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