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Title: Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose

Abstract

Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of /sup 51/CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for /sup 51/CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. modelmore » assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam
OSTI Identifier:
6273200
Resource Type:
Journal Article
Resource Relation:
Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States); Journal Volume: 5
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; KIDNEYS; BIOLOGICAL FUNCTIONS; BIOLOGICAL RADIATION EFFECTS; RADIATION INJURIES; BIOLOGICAL REPAIR; CHROMIUM 51; DOSE-RESPONSE RELATIONSHIPS; EDTA; FRACTIONATED IRRADIATION; ISODOSE CURVES; MICE; X RADIATION; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; BIOLOGICAL EFFECTS; BIOLOGICAL RECOVERY; BODY; CARBOXYLIC ACIDS; CHELATING AGENTS; CHROMIUM ISOTOPES; ELECTROMAGNETIC RADIATION; ELECTRON CAPTURE RADIOISOTOPES; EVEN-ODD NUCLEI; FUNCTIONS; INJURIES; INTERMEDIATE MASS NUCLEI; IONIZING RADIATIONS; IRRADIATION; ISOTOPES; MAMMALS; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; RADIATION EFFECTS; RADIATIONS; RADIOISOTOPES; RECOVERY; REPAIR; RODENTS; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals

Citation Formats

Stewart, F.A., Oussoren, Y., Luts, A., Begg, A.C., Dewit, L., Lebesque, J., and Bartelink, H. Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose. United States: N. p., 1987. Web. doi:10.1016/0360-3016(87)90297-5.
Stewart, F.A., Oussoren, Y., Luts, A., Begg, A.C., Dewit, L., Lebesque, J., & Bartelink, H. Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose. United States. doi:10.1016/0360-3016(87)90297-5.
Stewart, F.A., Oussoren, Y., Luts, A., Begg, A.C., Dewit, L., Lebesque, J., and Bartelink, H. Fri . "Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose". United States. doi:10.1016/0360-3016(87)90297-5.
@article{osti_6273200,
title = {Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose},
author = {Stewart, F.A. and Oussoren, Y. and Luts, A. and Begg, A.C. and Dewit, L. and Lebesque, J. and Bartelink, H.},
abstractNote = {Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of /sup 51/CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for /sup 51/CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.},
doi = {10.1016/0360-3016(87)90297-5},
journal = {Int. J. Radiat. Oncol., Biol. Phys.; (United States)},
number = ,
volume = 5,
place = {United States},
year = {Fri May 01 00:00:00 EDT 1987},
month = {Fri May 01 00:00:00 EDT 1987}
}
  • Multiple fraction experiments have been carried out to determine the response of mouse lung to repeated small doses of 240 kV X rays down to 150 rad/fraction using breathing rate and lethality to assess damage. Two experimental approaches were used to measure the effect of small doses in vivo: (1) multiple equal doses and (2) multiple priming doses followed by a large test dose. Analysis was performed using the multitarget two-component model and the linear test dose. The amount of repair was calculated as a function of either dose per fraction (F/sub R/) or total dose (F/sub rec/). Both F/submore » R/ and F/sub rec/ increased with decreasing dose per fraction but the change in F/sub R/ was small. The advantage of F/sub rec/ was that it varied more rapidly with dose per fraction than F/sub R/, so that possible differences between tissue repair capabilities are more visible on plots of repair as a function of dose per fraction. F/sub R/ and F/sub rec/ both decreased with the level of single-dose isoeffect injury; thus neither parameter is acceptable for comparing repair capability of different normal tissues with widely differing single-dose end point levels. Beta/alpha values were calculated and found to be a more acceptable index of repair capability than either F/sub R/ or F/sub rec/ because unlike those two parameters, ..beta../..cap alpha.. varied little with level of damage. Beta/alpha values of 1.7 to 4.2 krad/sup -1/ were obtained for both lung death and increased breathing rate and are clearly intermediate between the lower ..beta../..cap alpha.. ratios for acute reactions, i.e., skin and intestine, and the higher values for late reactions in kidney and spinal cord.« less
  • Two thousand four hundred mice were studied to determine the amount of irreparable injury induced as a function of the amount of the exposure dose. Approximately 3 to 17% of the exposure dose remained as irreparabie injury. (auth)
  • Data published previously have shown that repair of sublethal damage in mouse lung proceeds with two significantly different repair half-times of 0.4 h and 4.0 h and that the fast component has approximately four times more weight than the slow component. None of these data, however, were obtained after small dose fractions similar to those used in clinical radiotherapy. The purpose of the experiments presented here was to determine the half-time of the fast component only of repair in mouse lung after doses per fraction of 2.0 Gy. We irradiated the whole thoraces of mice with six equal doses ofmore » 2.09 Gy given at intervals ranging from 0 to 45 min. The dose was topped up 24 h later by a range of single doses designed to bring the response, i.e. breathing rate and death from pneumonitis, into the observable range. Data on breathing rate were converted into quantal response data. All data were analyzed by the linear-quadratic model that contains two rates of repair. The data showed that the repair rate is very rapid, giving a t{sub 1/2} ranging from 0.25 to 0.75 h for breathing rate and mortality, in agreement with our data published previously for higher dose fractions. There were no differences between the t{sub 1/2}`s obtained from the two assays of damage. These data indicate that the half-time of the fast component of repair in mouse lung is approximately 0.4 h after clinically relevant dose fractions. 12 refs., 2 figs., 2 tabs.« less