Cytotoxicity Of Hexavalent Chromate Compounds In Ch310t1/2 Cells And Cytomodulation By Sodium Arsenite And Methanol Extract Of Rauvolfia Vomitora (Afzel) In Mice.

ABSTRACT

Exposure to certain hexavalent chromate compounds (HCC) causes lung and colon cancers. Their mechanisms of cytotoxicity are unclear, but believed to be affected by ascorbate and particle size. However, their role is not clearly defined. Co-exposure with sodium arsenite (SA) is common, but its effect on HCC toxicity is unknown. Current therapy has side effects, necessitating the search for antidote from unexplored natural products such as Rauvolfia vomitora (RV). This study therefore investigates the effect of particle size and ascorbate on cytotoxity of selected HCC [lead chromate (PbCrO4), barium chromate (BaCrO4), strontium chromate (SrCrO4) and potassium dichromate (K2Cr2O7)] in C3H10T1/2 cells and cytomodulatory effects of SA and RV in mice. The effect of ascorbate, dehydroascorbate and particle size on HCC cytotoxicity in C3H10T1/2 cells was determined by measuring survival fraction and yield of foci by microscopy. Actin and cellular ultrastructure disruption and induction of cell death were assessed by electron and fluorescent microscopy. The molecular mechanisms of cytotoxicity and transformation were evaluated in eighty-four cell death genes using real time (RT2 ) gene array, while cell cycle analysis was done by flow cytometry. Leaves of RV were air dried, powdered and extracted with methanol. Forty male mice (20-25g) were divided into 8 groups of 5 Swiss albino mice each and treated with water (control), RV (275 mg/Kg), SA (2.5 mg/kg), K2Cr2O7 (12 mg/Kg), SA + K2Cr2O7, RV + SA, RV + K2Cr2O7, RV + SA + K2Cr2O7. Rauvolfia vomitora was given orally for seven days, while K2Cr2O7 and SA were administered on day seven. Serum aspartate and alanine aminotransferases (AST and ALT), catalase, glutathione-S-transferase (GST), glutathione and malondialdehyde (MDA) levels were determined by spectrophotometry. Micronucleated polychromatic erythrocytes (mPCEs) were evaluated by microscopy. Data were analysed using ANOVA and Student‟s t- test at p= 0.05.