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Dose-response and ultrastructural alterations in dioxane carcinogenesis.

1973; Pergamon Press; Volume: 9; Issue: 4 Linguagem: Inglês

10.1016/0014-2964(73)90088-1

1879-2995

Mary F. Argus, Rajindar S. Sohal, Georgia M. Bryant, Cornelia Hoch‐Ligeti, J. C. Arcos,

Genomics, phytochemicals, and oxidative stress

A dose-response study with dioxane revealed the hepatocarcinogenicity of this compound in male rats to be a function of the total oral dose administered. The progressive development of these tumors was studied histopathologically, and detailed electronmicroscopy was carried out on precancerous liver tissue and on hepatocellular carcinoma produced by dioxane. The LD50 dose of dioxane in male rats (5·60 g/kg body weight) is significantly decreased (5·18 g/kg) in animals pretreated with 3-methylcholanthrene. This suggests that a metabolite is involved in the toxicity and possibly carcinogenicity of dioxane, and that both may be potentiated by enzyme inducers. Because certain hydroperoxides are known to be carcinogenic, it was shown by micro-iodimetric titrations that the dioxane used does not contain a dioxane hydroperoxide and that no peroxide is formed under the conditions of administration.