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Effect of cis-Diamminedichloroplatinum(II) Combined with Whole Body Hyperthermia on Renal Injury¹

University of Texas, Medical School at Houston, Departments of Internal Medicine [J. W., F. R. S., J. M. C. B.] and Pathology [R. E. B.] and M. D. Anderson Hospital and Tumor Institute, Departments of Medical Oncology [R. A. N.], Radiobiology [E. L. T.], and Veterinary Medicine [L. C. S.], Houston, Texas 77030

The effect of whole body hyperthermia (WBH) on cis-diamminedichloroplatinum(II) (DDP) induced renal toxicity and antitumor effect was studied using a F344 rat model. Renal injury at 5 and 14 days after treatment was evaluated using animal mortality, renal functional assays (blood urea nitrogen, creatinine), and histopathological methods. WBH (120 min at 41.5°C) enhanced both antitumor effects and toxic side effects. The latter included increased mortality, increased blood urea nitrogen and creatinine levels, and increased renal damage. After simultaneous treatment with WBH and DDP, thermal enhancement ratios (TER) for renal damage between 2.5 and 3.0 were calculated. The histopathological changes observed in the kidney after DDP alone or combined with WBH were primarily found in the proximal pars recta tubules (S3 segment) in the outer stripe of the outer medulla. There was no qualitative difference in tubular damage between rats treated with DDP alone or those treated with DDP combined with WBH. However, at a fixed DDP dose, damage in the combined treatment modality group was significantly greater than in the DDP-only treated group.

¹ Supported by National Cancer Institute Grant RO1-CA-43090.

² On leave from Department of Radiotherapy, University of Amsterdam, Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

³ To whom requests for reprints should be addressed, at University of Texas, Health Sciences Center at Houston, Division of Oncology/Hematology, P.O. Box 20708, Houston, TX 77225.

Received 7/ 6/87. Revised 10/ 1/87. Accepted 10/19/87.