title: The influence of cisplatin on the response of mouse kidneys to multifraction irradiation.
abstract: 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.
authors.affiliation: Experimental Therapy, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
authors.forename: F A
authors.initials: FA
authors.lastname: Stewart
authors.forename: Y
authors.initials: Y
authors.lastname: Oussoren
authors.forename: H
authors.initials: H
authors.lastname: Bartelink
mesh_terms: 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
chemical_list: D011838:Radiation-Sensitizing Agents; D004247:DNA; D002945:Cisplatin