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Title: Sensitivity to Radiation-Induced Cancer in Hemochromatosis

Abstract

The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.

Authors:
;
Publication Date:
Research Org.:
Pacific Northwest National Lab., Richland, WA (US)
Sponsoring Org.:
USDOE Office of Environmental Management (EM) (US)
OSTI Identifier:
833475
Report Number(s):
EMSP-2000-69939
R&D Project: EMSP 69939; TRN: US200430%%1523
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: 1 Jun 2000
Country of Publication:
United States
Language:
English
Subject:
54 ENVIRONMENTAL SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; APOPTOSIS; DOSE-RESPONSE RELATIONSHIPS; HYBRIDIZATION; INDUCTION; IRON; LARGE INTESTINE; LIVER; MICE; NEOPLASMS; RADIATION DOSES; SENSITIVITY; TARGETS

Citation Formats

J, Bull Richard, and Anderson, Larry E. Sensitivity to Radiation-Induced Cancer in Hemochromatosis. United States: N. p., 2000. Web. doi:10.2172/833475.
J, Bull Richard, & Anderson, Larry E. Sensitivity to Radiation-Induced Cancer in Hemochromatosis. United States. doi:10.2172/833475.
J, Bull Richard, and Anderson, Larry E. Thu . "Sensitivity to Radiation-Induced Cancer in Hemochromatosis". United States. doi:10.2172/833475. https://www.osti.gov/servlets/purl/833475.
@article{osti_833475,
title = {Sensitivity to Radiation-Induced Cancer in Hemochromatosis},
author = {J, Bull Richard and Anderson, Larry E},
abstractNote = {The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.},
doi = {10.2172/833475},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2000},
month = {6}
}

Technical Report:

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