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.
- 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
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Cells
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DIGESTIVE SYSTEM
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
FRACTIONATED IRRADIATION
GASTROINTESTINAL TRACT
INTESTINES
IONIZING RADIATIONS
IRRADIATION
MAMMALS
MICE
ORGANS
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
RODENTS
SMALL INTESTINE
SURVIVAL CURVES
VERTEBRATES
X RADIATION