Exploration of the Transformation Potential of a Unique Male Rat Protein Alpha 2u -Globulin Using Hamster Embryonic Cells

Several environmentally and socially important chemicals such as d-limonene and unleaded gasoline have been demonstrated to induce alphas-globulin (a2u) nephropathy in male rats. Substantial progress has been made in characterizing the biological effects of these chemicals on the kidney and in further defining prerequisite events in the pathogenesis of this syndrome. The ot2u increase in the kidney is hypothesized to be the proximal event in the toxicologic and tumorigenic sequelae associated with administration of these xenobiolics over the male rat's lifetime rather than a direct effect of the administered chemical. The administered chemical appears to simply mediate the increase in ot2u concentration in the kidney. To further investigate the properties of a2u, this protein was tested in the pH 6.7 Syrian hamster embryo (SHE) cell transformation assay. The a2u caused morphological transformation in these cells, whereas another protein, bovine serum albumin, did not induce transformation at equimolar concentrations, suggesting a protein-specific phenomenon. Neither rf-limonene nor trimethylpentane (a causarcomponent in unleaded gasoline) induced SHE cell transformation. These results support the hypothesis that a2u increase in proximal convoluted tubules may directly cause renal tumorigenesis in male rats. The SHE cell transformation assay may be a useful tool for mechanistic studies of this syndrome.