Iron is essential for many cellular functions, but it is also a potent pro- oxidant that can produce hydroxyl radicals through Fenton chemistry. Ascorbic acid, a very potent scavenger of hydroxyl radicals, can enhance dietary, non- heme iron absorption by increasing the transfer of iron across the apical membrane of intestinal epithelial cells. In the presence of iron, in vitro experiments have shown ascorbic acid to act as a pro-oxidant. Whether ascorbic acid has pro-oxidant activity in vivo continues to be debated. Hereditary hemochromatosis (HH) is a common autosomal recessive disease in which the regulation of intestinal iron absorption is lost. The resulting iron overload is associated with excessive lipid peroxidation. The pattern of p53 mutations in HH is consistent with the mutagenic potential of the DNA adduct, l,N6-ethenodeoxyadenosine. The investigators hypothesize that despite the normal regulation of intestinal iron absorption, ascorbic acid and iron supplementation will lead to sufficient iron overload to increase lipid peroxidation and EdA formation. Furthermore, co-supplementation with iron and ascorbic acid in HH, in which regulation of intestinal iron absorption is lost, will result in worsening the iron overload leading to greater lipid peroxidation, EdA formation and hepatocellular carcinoma. The investigators propose experiments that are designed to examine the interactive effects of dietary iron and ascorbic acid and genetic iron overload on iron loading, lipid peroxidation and mutagenesis. They will use a mouse model of HH that is prone to hepatocellular formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Research Grants (R03)
Project #
5R03ES011487-02
Application #
6524846
Study Section
Special Emphasis Panel (ZES1-BKW-C (RO))
Program Officer
Packenham, Joan P
Project Start
2001-09-15
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$74,250
Indirect Cost
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618