Energy Citations Database

Bibliographic Citation

 
Document
For copies of Journal Articles, please contact the Publisher or your local public or university library and refer to the information in the Resource Relation field.
For copies of other documents, please see the Availability, Publisher, Research Organization, Resource Relation and/or Author (affiliation information) fields and/or Document Availability.
DOI http://dx.doi.org/10.1016/S0360-3016(01)01522-X
Title Selective radioprotection of hepatocytes by systemic and portal vein infusions of amifostine in a rat liver tumor model
Creator/Author Symon, Zvi E-mail: symonz@umich.edu ; Levi, Micha ; Ensminger, William D. ; Smith, David E. ; Lawrence, Theodore S
Publication Date2001 Jun 01
OSTI IdentifierOSTI ID: 20427931
Other Number(s)ISSN 0360-3016; IOBPD3 ; TRN: US02S0091010487
Resource TypeJournal Article
Resource RelationInternational Journal of Radiation Oncology, Biology and Physics ; VOL. 50 ; ISSUE: 2 ; PII: S036030160101522X; Copyright (c) 2001 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); PBD: 1 Jun 2001
Subject62 RADIOLOGY AND NUCLEAR MEDICINE ; APOPTOSIS; CARCINOMAS; CELL KILLING; HEPATOMAS; LIVER; RADIOPROTECTIVE SUBSTANCES
Description/Abstract Purpose: The tolerance of the liver to radiation is too low to permit an effective dose to be delivered to patients who have diffuse intrahepatic cancer. In this study we evaluated whether systemic or portal venous administration of the aminothiol compound, amifostine, could protect the normal liver from the effects of ionizing radiation without compromising tumor cell kill in a rat liver tumor model. Methods and Materials: Rats implanted with liver tumors were infused with 200 mg/kg amifostine over 15 min via the femoral or portal vein. The livers were irradiated with a single 6-Gy fraction 15-20 min after the termination of amifostine infusion. Protection of the liver was assessed by an in vitro hepatocyte micronucleus assay and tumor protection by an in vivo-in vitro clonogenic survival assay. Tissue levels of the active metabolite, free WR-1065, were determined in the tumor and in the normal liver using a specific HPLC assay with electrochemical detection. Results: After a 6-Gy fraction, the frequency of hepatocyte micronuclei after administration of saline, systemic amifostine, and portal venous amifostine was 18.7{+-}1%, 6.8{+-}1%, and 9.9{+-}2%, respectively, corresponding to a radiation equivalent effect of 6 Gy{+-} 0.5, 1.8 Gy{+-} 0.3, and 2.5 Gy{+-} 1.3, respectively. Both amifostine conditions showed considerably less radiation effect than saline-treated controls (p<0.01); the two amifostine conditions did not differ (p=0.3). The surviving fraction of tumor cells was not affected by amifostine treatment and was 0.03{+-}0.02 and 0.05{+-}0.03 for systemic and portal venous delivery and 0.06{+-}0.02 for control animals (ANOVA analysis showed no significant difference of the means p=0.34). Portal venous delivery produced significantly less WR-1065 in the tumor compared to systemic administration (54{mu}M{+-} 36 vs. 343{mu}M{+-} 88, respectively, p 0.03). Conclusions: Both systemic and portal venous administration of amifostine effectively protect hepatocytes from ionizing radiation without compromising tumor cell kill in a clinically relevant animal model. These findings suggest that amifostine may be a selective normal tissue radioprotectant in liver cancer and that regional/portal infusions may be preferable to systemic dosing.
Country of PublicationUnited States
LanguageEnglish
Formatpage(s) 473-478
System Entry Date2004 Feb 23

Top