RESUMO
Iron-enriched diets caused an increase of tumor rate in two models of dimethylhydrazine(DMH)-induced colon tumorigenesis in mice. The effect was independent of the time the iron-diet was fed, i.e. during DMH-treatment or following the DMH-treatment period. The increase of tumor rate depended on the iron concentration in the diet (0.5-3.5%). The concentration-dependent iron accumulation in the colonic mucosa of mice was paralleled by increments of malonaldehyde contents indicating lipid peroxidation, another factor known to be involved in tumor development. It is suggested that iron exerts cocarcinogenic activity in the DMH-model by stimulating cell proliferation and inducing oxidative stress in the colonic mucosa. This effect of iron is independent of the time of tumor-initiation by DMH, as it is also observed in the period of tumor-promotion/progression after DMH-treatment.
Assuntos
Cocarcinogênese , Neoplasias do Colo/induzido quimicamente , Alimentos Fortificados/toxicidade , Ferro/toxicidade , Neoplasias Retais/induzido quimicamente , Animais , Neoplasias do Colo/patologia , Dieta/efeitos adversos , Mucosa Intestinal/química , Ferro/análise , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos , Monometilidrazina , Neoplasias Retais/patologiaAssuntos
Carcinógenos/toxicidade , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Dimetilidrazinas/toxicidade , Ferro/toxicidade , Neoplasias Retais/induzido quimicamente , 1,2-Dimetilidrazina , Animais , Testes de Carcinogenicidade , Linhagem Celular , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Humanos , Ferro/análise , Masculino , Camundongos , Camundongos Endogâmicos , Neoplasias Retais/patologiaRESUMO
Feeding mice diets containing different amounts of Fe-fumarate over a period of 4 weeks resulted in a dose-dependent increase of iron concentrations in liver as well as proximal and distal colon. In parallel, a dose-dependent increase in lipid peroxidation was observed in these organs; both effects were well correlated. No significant effects were seen in other organs (lung, heart, brain or kidney). As dietary iron was shown to enhance dimethylhydrazine-induced colon carcinogenesis in mice, it is concluded that oxygen activation and lipid peroxidation might be involved in colon tumorigenesis and cell proliferation.