Unilateral kidney irradiation and late retreatment with cis-dichlorodiammineplatinum (II): functional measurements with 99mtechnetium-dimercaptosuccinic acid.
A rat model was used to study renal function after unilateral kidney irradiations. The left kidney was irradiated with a single dose (6-14 Gy), 2 equal sized fractions (10-16 Gy total dose) or 4 equal sized fractions (12 to 21 Gy total dose). At regular time intervals after treatment, the left kidney function was assessed with the use of 99mTc-Dimercaptosuccinic acid for a period of about 1 year. It was found that renal function declined in a dose- and time-dependent manner. The threshold dose for detecting functional impairment was 8 Gy for 1 fraction, 12 Gy for 2 fraction and 15 Gy for 4 fraction irradiations, demonstrating the sensitivity of the isotope tracer test used in these experiments. Retreatment of the rats with a single i.p. dose of 5 mg/kg cis-Dichlorodiammineplatinum (II) (cis-DDP) given at about 1 year after X ray exposure revealed an important relative decrease in the function of the irradiated compared to the unirradiated kidney. Reductions in function of 11 to 70% (depending on radiation dose and schedule) compared with control values were observed at 11 weeks after drug injection. These results demonstrate that a previously irradiated kidney is more sensitive to a subsequent treatment with cis-DDP than the contralateral hypertrophied kidney in the same animal.
Landuyt
W
W
Department of Experimental Radiotherapy, University Hospital St. Rafaël, Leuven, Belgium.
Van der Kogel
A J
AJ
De Roo
M
M
Hoogmartens
M
M
Ang
K K
KK
van der Schueren
E
E
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D009942:Organometallic Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D004113:Succimer; D013438:Sulfhydryl Compounds; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D013997:Time Factors
D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D004113:Succimer; D002945:Cisplatin