Renal damage in mice after treatment with cisplatin and x-rays: comparison of fractionated and single-dose studies

Journal Article · Fri Jan 01 04:00:00 EST 1988 · NCI Monogr.; (United States)

OSTI ID:6936698

Stewart, F A; Luts, A; Oussoren, Y; Begg, A C; Dewit, L; Bartelink, H

Functional kidney damage in mice was measured after bilateral irradiation with x-rays alone or in combination with cisplatin (c-DDP). A single drug dose (6 mg/kg) was injected 30 minutes before the first of four or eight x-ray doses, given as four fractions per day with a minimum interval of 5 hours between treatments. A 30-fraction schedule was also investigated, with 15 fractions given in the first week (3 fractions per day), followed by a 2-week rest period and another 15 fractions in the fourth week. The c-DDP (4 mg/kg) was administered 30 minutes before the first fraction of each week, giving a total drug dose of 8 mg/kg. Renal function was assessed monthly from 10 to 37 weeks after the start of treatment by the clearance of /sup 51/Cr-labeled EDTA. The combined treatment caused more kidney damage than either agent alone for all fractionation schedules. Enhancement of the radiation damage by c-DDP changed only slightly with fractionation; dose enhancement factors were 1.2 for 1 fraction to 1.3 for 30 fractions. Modeling studies showed that this was consistent with the additive toxic effects of the two agents. There was no change in the alpha/beta for renal damage after x-rays plus c-DDP, compared with x-rays alone (alpha/beta = 1.9 Gy), implying that there was no reduction in repair and no modification of the x-ray response by c-DDP.

• Research Organization: The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam
• OSTI ID: 6936698
• Journal Information: NCI Monogr.; (United States), Journal Name: NCI Monogr.; (United States) Vol. 6; ISSN NCIME
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ACUTE IRRADIATION
AMINO ACIDS
ANIMALS
ANTINEOPLASTIC DRUGS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MODELS
BODY
CARBOXYLIC ACIDS
CHELATING AGENTS
CHROMIUM 51
CHROMIUM ISOTOPES
COMBINED THERAPY
COMPARATIVE EVALUATIONS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EDTA
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
FRACTIONATED IRRADIATION
INJURIES
INTERMEDIATE MASS NUCLEI
IONIZING RADIATIONS
IRRADIATION
ISOTOPES
KIDNEYS
MAMMALS
MICE
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RADIATIONS
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
RODENTS
THERAPY
VERTEBRATES
X RADIATION