RESUMO
Fatty acid hydroperoxides are produced from unsaturated fatty acids in the presence of oxygen at elevated temperatures during food processing. Their effects on gene expression in colorectal tumour cells were studied using linoleic acid hydroperoxide (LOOH) as a model compound. Addition of LOOH to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide. Both cell lines were observed to increase VEGF factors based on mRNA. High consumption of dietary fat promotes colon carcinogenesis in the long-term. While this effect is well known, the underlying mechanisms are not understood. An approach was made starting from the assumption that LOOH is present in dietary fats as a result of heating. LOOH undergoes homolytic cleavage in the presence of iron. Various radicals are formed on mixing LT97 or SW480 cells with LOOH. The expression of tumour-promoting factors was inhibited by caroverine and ubiquinone, which may be justified as active chemopreventive agents.
Assuntos
Anticarcinógenos/farmacologia , Neoplasias do Colo/prevenção & controle , Ácidos Linoleicos/antagonistas & inibidores , Peróxidos Lipídicos/antagonistas & inibidores , Quinoxalinas/farmacologia , Ubiquinona/farmacologia , Adenoma/genética , Adenoma/metabolismo , Antioxidantes/farmacologia , Carcinoma/genética , Carcinoma/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/etiologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Ácido Linoleico/administração & dosagem , Ácido Linoleico/metabolismo , Ácidos Linoleicos/administração & dosagem , Ácidos Linoleicos/metabolismo , Ácidos Linoleicos/toxicidade , Peróxidos Lipídicos/administração & dosagem , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/toxicidade , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Viral hepatitis (VH) is an inflammatory reaction of the liver to hepatotropic viruses. Acute VH can be classified according to the virus and type of necrosis. Chronic hepatitis (CH) might be active, persistent or lobular based on previous classification. More recently the grade (necroinflammatory activity) and stage (fibrosis and architectural distorsion) of CH have been distinguished and scored. Apoptosis and necrosis probably coexist in VH and contribute to hepatocyte death. Several "death factors", such as transforming growth factor b, Apo1/Fas and tumor necrosis factor play a role in the execution of cell death. Injury of hepatocytes during viral infection can occur as a direct effect of the virus or as a result of the host immune response. Expression of different viral antigens can be detected during VH and might be visualized. Phenotyping of the portal inflammatory cell infiltrate in CH has shown a T-cell zone comprised of CD4+ helper T cells and CD8+ supressor/cytotoxic T cells at the periphery of the lobules. The pathogenetic mechanisms responsible for the final outcome of viral infection depend on viral factors (such as genotype, mutation etc.), virus-host interaction, expression of viral protein, several cytokines etc. which finally lead to the well known histological alterations of viral hepatitis.
