The influence of cisplatin on the response of mouse kidneys to multifraction irradiation.
The aim of these studies was to measure the extent of renal damage after fractionated irradiation in combination with cis-diamminedichloroplatinum(II) (c-DDP) and to determine whether there was any drug-induced inhibition of repair of sublethal X-ray damage. Fractionated irradiations were given either in a short overall treatment time of 2 days or in a total time of one month, in which irradiations were given in the first and fourth weeks only. A single dose of c-DDP was given before the first X-ray dose for treatments in a total time of 2 days and before the first X-ray dose of each week for the split-course treatments. Renal function was measured at monthly intervals (from 18 to 39 weeks after the start of treatment) by clearance of 51Cr-EDTA. The renal damage was always worse after combined treatments (X + c-DDP) than after X-rays alone. A comparison of radiation dose-response curves with and without c-DDP yielded Dose Enhancement Factors (DEFs) of 1.2 to 1.4 for all fractionation schedules, with no trend for an increase in DEF with increasing number of fractions. A Linear-Quadratic (LQ) analysis of the data demonstrated that there was no change in the alpha/beta value for renal radiation damage for the combined treatments compared with X-rays alone (alpha/beta = 2-3 Gy). These results suggest that the increased renal damage which occurred after combined X + c-DDP was due to independent, additive toxicities and not to radiosensitization or inhibition of X-ray repair by the drug.
Stewart
F A
FA
Experimental Therapy, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Oussoren
Y
Y
Bartelink
H
H
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007668:Kidney / Q000528:radiation effects*; D007677:Kidney Function Tests; D051379:Mice; D008809:Mice, Inbred C3H; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D004247:DNA; D002945:Cisplatin