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Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice

Journal Article · · Radiat. Res.; (United States)
DOI:https://doi.org/10.2307/3576930· OSTI ID:5848965

The effect of cis-diamminedichloroplatinum (II) (c-DDP) on the shape of the radiation dose-response curve for mouse duodenal crypt cells was investigated. A priming X-ray dose was followed 18 h later by graded test doses (single doses or five equal fractions at 3-h intervals) with or without c-DDP. Curves were fitted by a linear quadratic (LQ) relationship. The drug modified the dose-response curve by enhancing both the alpha and the beta terms. Repair kinetics were analyzed in split-dose experiments. c-DDP caused a minor, nonsignificant decrease in the rate of repair after irradiation. The survival ratio after split-dose irradiation, when the same X-ray doses were given, was actually slightly increased by the drug. This paradoxical effect can be explained by the fact that c-DDP mainly increased the beta term in the LQ relationship. There was no significant increase in crypt cell survival when split-drug doses were given alone at increasing intervals, suggesting no cellular repair after c-DDP treatment. The data are discussed in the light of the recently proposed lethal and potentially lethal (LPL) unified repair model of Curtis.

Research Organization:
Antoni van leeuwenhoek Huis, Amsterdam, Netherlands
OSTI ID:
5848965
Journal Information:
Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 111:3; ISSN RAREA
Country of Publication:
United States
Language:
English