Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice.
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.
Dewit
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L
Department of Experimental Radiotherapy, Antoni van leeuwenhoek Huis, Amsterdam.
Oussoren
Y
Y
Hart
G
G
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004386:Duodenum / Q000187:drug effects / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D012107:Research Design; D014965:X-Rays
D002945:Cisplatin