Protracted treatment of C57B1 mice with Zn-DTPA after 241Am injection reduces the long-term radiation effects.
Repeated intraperitoneal injections of ZnNa3-diethylenetriaminepenta-acetate (ZnDTPA), once a week, during 8 successive weeks, and starting 4 days after injection of 58 and 373 kBq 241Am/kg to C57B1 mice, were an effective protection against long-term radiation damage. At both dose levels of 241Am, Zn-DTPA reduced the 241Am concentration in bones by between 33% and 45%, and in the liver by 97%. Mean survival with 241Am was shortened in Zn-DTPA-treated mice, by 17% at the lower dose level and by 70% at the higher dose level. After treatment with DTPA at the lower 241Am level, survival became equal to that of control mice without 241Am, while at the higher level life span was still shortened. After the lower 241Am dose the incidence of bone tumours, liver carcinomas and the total number of all malignant tumours were significantly reduced by chelation therapy. The decrease in bone tumour incidence was proportional to the decrease in 241Am concentration and reduction in cumulative radiation dose in bone after chelation therapy. The incidence of liver carcinomas was reduced to that in non-241Am-injected mice and the reduction was thus proportional to the 97% reduction in 241Am concentration of the liver at the end of chelation therapy. After the higher 241Am dose no tumours showed up in sham-treated mice, probably due to the overkill effect on the cells at risk. In the corresponding Zn-DTPA-treated mice, bone tumours and a few other malignant tumours were observed.
Radionuclide Metabolism Section, SCK-CEN, Department of Radioprotection, Mol, Belgium.
G E
GE
Schoeters
J R
JR
Maisin
O L
OL
Vanderborght
D000576:Americium / Q000633:toxicity*; D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D004307:Dose-Response Relationship, Radiation; D004353:Drug Evaluation, Preclinical; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D004369:Pentetic Acid / Q000627:therapeutic use*; D011837:Radiation-Protective Agents; D013997:Time Factors
D011837:Radiation-Protective Agents; D004369:Pentetic Acid; D000576:Americium