Proliferative defects in renal and intestinal epithelium after cis-dichlorodiammine platinum (II)

The effects of cis-dichlorodiammine platinum II (DDP) on the intestinal mucosa and the kidney were studied after single and multiple treatments with intervals of 7-45 days. After a single treatment, the jejunal epithelium underwent a transient interruption of cell proliferation followed by a hyperplastic recovery and return to control proliferative rate on Day 7. Subsequent treatments led to suboptimal recovery for all treatment intervals. In contrast, DDP induced a 6-fold increase in [3H]dT incorporation in the kidney by Day 7 which remained high until Day 21, and returned to near-control values by Day 45. After a single DDP treatment, the "recovery potential" of kidneys, measured by the proliferative response to folic-acid stress, demonstrated suboptimal proliferative reserve compartments for up to 45 days. The distinction between acute and delayed sensitivity to subsequent drug treatment was more apparent in the DDP-treated kidney than in the intestinal epithelium.