Sensitivity to Radiation-Induced Cancer in Hemochromatosis

Technical Report · Thu Jun 01 00:00:00 EDT 2000

DOI:https://doi.org/10.2172/833475· OSTI ID:833475

J, Bull Richard; Anderson, Larry E

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.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE Office of Environmental Management (EM) (US)
• OSTI ID: 833475
• Report Number(s): EMSP-2000-69939; R&D Project: EMSP 69939; TRN: US200430%%1523
• Resource Relation: Other Information: PBD: 1 Jun 2000
• Country of Publication: United States
• Language: English

Related Subjects

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