Mitomycin C-induced organ toxicity in Wistar rats: a study with special focus on the kidney

Two studies were performed to investigate acute and chronic organ toxicity after Mitomycin C (MMC) administration in Wistar rats. Six rats received 2.5 mg/kg MMC i.p. once and were followed for 5 consecutive days. The alanine aminopeptidase (AAP)/creatinine ratio increased significantly, compared to a control group receiving saline. Four groups of rats were injected i.p. weekly for 5 weeks; 6 control rats with saline, 7 rats with 1.7 mg/kg of MMC, 7 rats with 10 mg/kg 5-fluorouracil (5-FU) and 7 rats with MMC as well as 5-FU. The latter two groups were included to study possible toxicity synergism between the two drugs. A significant decrease in AAP excretion in the MMC group, as well as a nonsignificant decrease in the MMC/5-FU group were the most remarkable observations. Light microscopy did not show renal changes, but did not show alveolar septal congestion after repeated MMC injections. It is concluded that MMC causes tubular damage in Wistar rats, with acute leakage of enzyme from the cells, followed by enzyme depletion during chronic treatment. Also MMC induces pulmonary changes in Wistar rats. To what extent these changes represent early stages of toxicity remains to be elucidated.