Experiments were conducted to evaluate critically the role of vitamin A in the maintenance and functional integrity of mucus-secreting goblet cells in rat small intestine. Essentially synchronous vitamin A deficiency was induced by the withdrawal of retinoic acid from mature, stringently-deficient male rats reared by feeding vitamin A-depleted weanlings diets first supplemented with and then lacking in 2 micrograms retinoic acid per gram diet in repeating 18 day:10 day cycles. Secondary inanition was minimized by force-feeding both deficient and control animals twice daily. Whereas the prevalence of oligomucus cells was unchanged, the number of goblet cells per duodenal crypt gland decreased abruptly to 60% of control values starting 2 to 3 days after the withdrawal of retinoic acid and then stabilized. The responses of mucus-secreting cells to atropine and pilocarpine were identical in vitamin A deficient and control animals. As studied with [3H]thymidine, the rate of division of epithelial cells and the migration rate of columnar and goblet cells out of the crypt gland and along the villus were also unaffected by vitamin A deficiency. We conclude that two populations of goblet cells exist in the intestine--one relatively insensitive and the other sensitive to vitamin A status. In vitamin A deficiency, the rate of differentiation of sensitive goblet cells from oligomucus cells and other precursor cells seems to be blocked.
para-Phenylenediamine (p-PD), a widely used aromatic amine in the preparation of commercial oxidative-type hair dyes, has been previously demonstrated to have neither mutagenic activity to Salmonella typhimurium nor carcinogenic activity in rats and mice. In this study, the mutagenicity of p-PD after an oxidation by hydrogen peroxide towards S. typhimurium TA98 and its carcinogenicity in Wistar rats were examined both by topical application to the shaved skin and by s.c. injection. The oxidation product was found to be strongly mutagenic to the bacterial tester strain in the presence of rat liver S-9 fraction. Interestingly, in female rats, both topical application and s.c. injection for 18 months of oxidized p-PD could induce a statistically significant incidence of mammary gland tumors (greater than 50%, P less than 0.05). In addition, uterine tumors and soft tissue tumors of both malignant and benign types were also significantly induced (43% and 57%, P less than 0.05) in the s.c. injection group. On the other hand, tumors of mammary gland and soft tissue were not observed in male rats under similar experimental conditions. However, tumors of other organs including liver, kidney, adrenal gland, thyroid gland, urinary bladder and lung were occasionally observed in male rats of both groups and might be related to the p-PD treatment.
Protein-thiol groups that react with dihydroxydinaphthyl disulphide during a 7 h incubation (so-called reactive protein thiols, PSH,) have been quantitatively measured on sections of human uterine cervix by microcytospectrophotometry.Measurements were made on areas (1 pmz) of epithelium and adjoining stroma in samples of normal cervix, and in samples obtained from patients with dysplasia, carcinoma-in-situ and invasive cancer. The ratio of PSH, in epithelium to stroma is substantially reduced in the pathological conditions compared with normal and in apparently normal adjacent areas. Such changes in PSH, are discussed in relation to the redox balance of the tissue, and free radical disturbances previously described.
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