RESPONSE OF THE MURINE GASTRO-INTESTINAL EPITHELIUM TO CIS-DICHLORODIAMMINEPLATINUM-II - RADIATION COMBINATIONS

Single doses of cis-dichlorodiammineplatinum II (cis DDP) up to 8 mg/kg produced a dose-dependent inhibition of proliferative activity with a subsequent period of compensatory hyperplasia in the colon. The stomach was less responsive to cis DDP. Cis DDP-radiation combinations produced a dimunition in the proliferative response of the colon when compared to that following radiation only. This response was only seen in the stomach following 8 mg/kg of cis DDP and radiation. Cytokinetic analysis of the jejunal response to 8 mg/kg of cis DDP showed a gradual reduction in LN and MF/crypt with a reduction in the rate of DNA synthesis of S-phase cells through 8 hours post-treatment. By 24 hours the cellular DNA synthetic rate had recovered, although the number of S-phase cells was further reduced. The previously reported jejunal response to cis DDP-radiation combinations involved a reduction in crypt survival, coupled with a reduced proliferative capacity of surviving cells. Further investigation has revealed a possible inhibition of radiation damage repair by cis DDP, leading to increased levels of cell kill with the combination and reduced recovery of DNA synthetic rates in surviving cells. © 1979.