Abstract
2, 2, 4-Trimethylpentane (TMP) was administered orally to male Sprague-Dawley rats for 26 weeks to induce α2u-globulin nephropathy and histopathological examinations of the kidney as well as urinary sediment morphology and 5-bromo-2'-deoxyuridine (BrdU) incorporation were performed. The number of exfoliated renal epithelial cells in the urine increased with the TMP treatment until week 4, when a peak of approximately 90-fold as compared with the matched control values was observed. Significantly elevated levels then persisted throughout the study. Deposits of α2u-globulin and BrdU labeling in the kidney also reached maxima at week 4. A correlation among the amount of α2u-globulin deposits, the BrdU labeling indices, and the numbers of exfoliated cells in the urine was noted at each time point. The results thus suggest that damaged cells become detached following excessive accumulation of α2u-globulin and this stimulates regenerative cell proliferation in the kidney. Quantitative examination of exfoliated cells in the urine may thus provide a reliable estimate of cell proliferation induced by α2u-globulin nephropathy during rat toxicology studies.
