The Effect of Iron Overload on the Long-term Toxicological Effects of Fumonisin B1 in Rat Liver
type: CreativeWork
description: The long-term toxicological effects of hepatic iron overload on the cancer initiating and promoting properties of fumonisin B1 (FB1) were investigated in male Fisher 344 rats. An initial pilot (dose response) study over 15 weeks was performed to determine a level of dietary iron that achieves a high hepatic iron concentration in the absence of significant side effects, to be used in the subsequent long-term carcinogenesis study with FB1. Doses of 1%, 1.5% and 2% dietary carbonyl iron (Fe) were used for 10 weeks, followed by a level of 0.5% Fe for another 5 weeks. After 10 weeks of feeding 1% Fe, the hepatic iron level was 30-fold that of controls. Following the reduction in dietary iron to 0.5%, the hepatic iron level was maintained and side effects were minimal. Irrespective the dose of iron, the iron deposition was initially confined to zone 1 (periportal region), but with increased iron loading, extended to zone 2 (mid-zonal region) and zone 3 (perivenular region). Iron overload was shown to increase hepatocellular proliferation as seen in labelling of cells with 5-bromo-2’-deoxy-uridine (BrdU). Lipid peroxidation, measured as MDA, was also significantly enhanced by excess iron and levels correlated the iron dosage. In the long-term study, half of the rats were submitted to an iron-loading regimen with 1% Fe for 10 weeks, while the other half received the powdered AIN-93M diet only. The iron was then reduced to 0.5%; the rats were divided into four treatment groups: FB1/Fe (n=15); Fe (n=14); FB1/AIN (n=15); and control group (n=15), respectively. FB1 was fed at 250 mg/kg AIN-93M diet for 5 weeks, followed by 100 mg/kg for 20 weeks. The effect of iron on FB1-induced initiation and promotion was assessed in 5 rats from each group at week 35. FB1 was removed from the diet of the remaining rats but iron supplementation continued for 25 weeks. The rats were terminated and the effect of dietary iron on the progression phase of FB1-induced carcinogenesis was assessed. T…
abstract: The long-term toxicological effects of hepatic iron overload on the cancer initiating and promoting properties of fumonisin B1 (FB1) were investigated in male Fisher 344 rats. An initial pilot (dose response) study over 15 weeks was performed to determine a level of dietary iron that achieves a high hepatic iron concentration in the absence of significant side effects, to be used in the subsequent long-term carcinogenesis study with FB1. Doses of 1%, 1.5% and 2% dietary carbonyl iron (Fe) were used for 10 weeks, followed by a level of 0.5% Fe for another 5 weeks. After 10 weeks of feeding 1% Fe, the hepatic iron level was 30-fold that of controls. Following the reduction in dietary iron to 0.5%, the hepatic iron level was maintained and side effects were minimal. Irrespective the dose of iron, the iron deposition was initially confined to zone 1 (periportal region), but with increased iron loading, extended to zone 2 (mid-zonal region) and zone 3 (perivenular region). Iron overload was shown to increase hepatocellular proliferation as seen in labelling of cells with 5-bromo-2’-deoxy-uridine (BrdU). Lipid peroxidation, measured as MDA, was also significantly enhanced by excess iron and levels correlated the iron dosage. In the long-term study, half of the rats were submitted to an iron-loading regimen with 1% Fe for 10 weeks, while the other half received the powdered AIN-93M diet only. The iron was then reduced to 0.5%; the rats were divided into four treatment groups: FB1/Fe (n=15); Fe (n=14); FB1/AIN (n=15); and control group (n=15), respectively. FB1 was fed at 250 mg/kg AIN-93M diet for 5 weeks, followed by 100 mg/kg for 20 weeks. The effect of iron on FB1-induced initiation and promotion was assessed in 5 rats from each group at week 35. FB1 was removed from the diet of the remaining rats but iron supplementation continued for 25 weeks. The rats were terminated and the effect of dietary iron on the progression phase of FB1-induced carcinogenesis was assessed. T…
author: Werner, Denise
date published: 2002-07-19
date modified: 2026-07-24T02:51:33Z
provider: Ludwig Maxmilians Universität München
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Ludwig-Maximilians-Universität