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-lim onene and unleaded gasoline have been demonstrated to induce alpha(2u) -globulin (alpha 2u) nephropathy in male rats. Substantial progress ha s been made in characterizing the biological effects of these chemical s on the kidney and in further defining prerequisite events in the pat hogenesis of this syndrome. The alpha 2u increase in the kidney is hyp othesized to be the proximal event in the toxicologic and tumorigenic sequelae associated with administration of these xenobiotics over the male rat's lifetime rather than a direct effect of the administered ch emical. The administered chemical appears to simply mediate the increa se in alpha 2u concentration in the kidney. To further investigate the properties of alpha 2u, this protein was tested in the pH 6.7 Syrian hamster embryo (SHE) cell transformation assay. The alpha 2u caused mo rphological transformation in these cells, whereas another protein, bo vine serum albumin, did not induce transformation at equimolar concent rations, suggesting a protein-specific phenomenon. Neither d-limonene nor trimethylpentane (a causal component in unleaded gasoline) induced SHE cell transformation. These results support the hypothesis that al pha 2u increase in proximal convoluted tubules may directly cause rena l tumorigenesis in male rats. The SHE cell transformation assay may be a useful tool for mechanistic studies of this syndrome.