Dietary iron enhances the tumor rate in dimethylhydrazine-induced colon carcinogenesis in mice.
Treatment of male mice with 20 mg/kg dimethylhydrazine (DMH) s.c. for 10 weeks caused a mean tumour rate of 3.5 after 20 weeks. Dietary iron (3.5% Fefumarate for 10 weeks) enhanced the mean tumour rate to 13.9. All tumours detected were localized exclusively in the distal colon and rectum. The iron load caused a 6.5-fold increase in the mucosal Fe-concentration in the proximal as well as distal colon. DMH-demethylase activity was not influenced by iron and did not differ between proximal and distal segments. Cytosolic alcohol dehydrogenase (ADH) activity was also not altered by iron, but was 3.3-fold higher in the distal colon and rectum as compared to proximal segments; this might explain the DMH-induced tumorigenesis in the distal colon only. It is suggested that iron ions might evoke cocarcinogenic activity by a stimulation of cell proliferation.
Siegers
C P
CP
Institute of Toxicology, Medical University of Lübeck, F.R.G.
Bumann
D
D
Baretton
G
G
Younes
M
M
D000426:Alcohol Dehydrogenase / Q000032:analysis; D000818:Animals; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced*; D003676:Deferoxamine / Q000494:pharmacology; D004032:Diet; D004127:Dimethylhydrazines; D005260:Female; D007501:Iron / Q000494:pharmacology*; D051379:Mice
D004127:Dimethylhydrazines; D007501:Iron; D000426:Alcohol Dehydrogenase; D003676:Deferoxamine