Tolerance of previously irradiated mouse kidneys to cis-diamminedichloroplatinum(II)

In this study the tolerance of previously irradiated kidneys to retreatment with chemotherapy was assessed. cis-Diamminedichloroplatinum(II) (c-DDP) was given to groups of mice at 1, 3, or 6 months after bilateral renal irradiation with single doses of 8-14 Gy. Renal function was measured monthly (by clearance of 51Cr ethylenediaminetetraacetic acid) from 4-35 weeks after c-DDP injection and results were compared with function after X-rays alone or drug alone. At early testing times (during the first 11 weeks after c-DDP injection) the renal function of mice given drug at 1 or 3 months after irradiation was very similar to that seen after drug alone. c-DDP given at 6 months caused slightly more damage than either drug or X-rays alone, but these results could be explained in terms of additive toxicities. At later testing times (11-35 weeks after c-DDP injection), renal function was much worse in all animals which had received previous irradiation, with the greatest damage when c-DDP was given 6 months after X-rays. This may be partly due to additional cell killing by the drug causing the expression of subclinical radiation injury. It is also possible that c-DDP pharmacokinetics was altered in animals with previously irradiated kidneys, leading to higher drug exposures in these mice.