The influence of cisplatin on the response of mouse kidneys to multifraction irradiation. 1989

F A Stewart, and Y Oussoren, and H Bartelink
Experimental Therapy, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.

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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007677 Kidney Function Tests Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine. Function Test, Kidney,Function Tests, Kidney,Kidney Function Test,Test, Kidney Function,Tests, Kidney Function
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D011829 Radiation Dosage The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv). Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D011838 Radiation-Sensitizing Agents Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells. Radiation Sensitizer,Radiosensitizing Agent,Radiosensitizing Agents,Agents, Radiation-Sensitizing,Radiation Sensitizers,Radiation Sensitizing Agents,Radiation-Sensitizing Drugs,Radiation-Sensitizing Effect,Radiation-Sensitizing Effects,Radiosensitizing Drugs,Radiosensitizing Effect,Radiosensitizing Effects,Agent, Radiosensitizing,Agents, Radiation Sensitizing,Agents, Radiosensitizing,Drugs, Radiation-Sensitizing,Drugs, Radiosensitizing,Effect, Radiation-Sensitizing,Effect, Radiosensitizing,Effects, Radiation-Sensitizing,Effects, Radiosensitizing,Radiation Sensitizing Drugs,Radiation Sensitizing Effect,Radiation Sensitizing Effects,Sensitizer, Radiation,Sensitizers, Radiation,Sensitizing Agents, Radiation
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D005260 Female Females

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