Abnormal patterns of mucus secretion in apparently normal mucosa of large intestine with carcinoma

178

Summary.-Our previous studies, in specimens of large intestine resected for carcinoma, have shown abnormal patterns of mucous secretion in areas of apparently " normal " mucosa, where goblet cells produce mainly sialomucins as compared with the true normal colonic mucosa in which sulphomucins predominate. In the present work, large bowel cancer was induced in rats by the administration of 1,2-dimethylhydrazine-2HCl (DMH). We attempted to study the sequential histological and secretory abnormalities which developed in the colonic epithelium during carcinogenesis, and to correlate these changes with those described above in the human. The microscopical and histological lesions observed in the colonic mucosa of DMH treated rats confirmed the findings of other authors and resembled the human colorectal cancer. The earliest changes detected were small foci of hyperplasia accompanied from the 6th week onwards by several foci of dysplasia. Carcinoma in situ appeared at the 15th week and finally invasive carcinoma developed from the 19th week onwards. Changes in the type of mucous secretion, with predominance of sialomucins, were observed in the majority of the areas showing mild to moderate dysplasia whilst the surrounding normal epithelium produced sulphated material. Mucous depletion was a common feature in areas of severe dysplasia and carcinoma.These findings correlated well with the similar variations in the mucin composition observed in human colonic mucosa in carcinoma and further supported our previous hypothesis that mucin changes characterized by an increase in sialomucins might reflect early malignant transformation. If this hypothesis proved to be correct, the use of a simple method for the identification of mucins in large bowel biopsies would be of great help in detecting early malignancy.

mentioning

confidence: 98%

Mucous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study

Filipe¹

1975

178

“…The timing of the bypass operation in relation to azoxymethane treatment and the degree of resultant weight loss seem to be critical factors in the development of tumours Williamson, 1980) and may partly explain why colon cancer has not yet been reported after jejunoileal bypass for obesity in man. Filipe has postulated that an increase in sialomucins, which she found to correlate with the presence of epithelial dysplasia in man and the rat, might represent early malignant transformation of the colonic mucosa (Dawson & Filipe, 1976;Filipe, 1975;Filipe & Branfoot, 1974;Filipe et al, 1982). Our own findings call this hypothesis into question.…”

Section: Discussionmentioning

confidence: 74%

“…There is general agreement that the premalignant colonic epithelium of the rat shows an increased number of goblet cells containing sialomucins, and both Filipe and Shamsuddin have described a similar pattern in the "normal" colonic mucosa of patients with carcinoma of the large bowel (Dawson & Filipe, 1976;Filipe & Branfoot, 1974;. Hyperplasia of goblet cells containing sialomucin is particularly marked in the distal colon, where azoxymethane-induced carcinomas most frequently arise .…”

Section: Discussionmentioning

confidence: 90%

Goblet cell changes during intestinal adaptation to azoxymethane and enteric bypass in the rat

Io¹,

Bristol²,

Williamson³

1985

Summary Numbers of intestinal goblet cells containing specific acid mucins were determined in male Sprague-Dawley rats receiving azoxymethane (total dose 90mg kg-1) with or without jejunoileal bypass (JIB). Controls During the latent period of experimental colonic carcinogenesis, changes occur in the relative proportions of specific acid mucins elaborated by the goblet (mucous) cells. Twenty weeks after exposure to azoxymethane or dimethylhydrazine, rats show a substantial increase in the number of goblet cells containing sialomucins as opposed to sulphomucins (Filipe, 1975;. A similar and largely specific hyperplasia of sialomucin cells characterises the adaptive response of the colon and functioning jejunoileum to subtotal enteric bypass, as performed for morbid obesity in man (Olubuyide et al., 1984). Since this operation stimulates neoplasia as well as hyperplasia in rat large intestine , the distribution of acid mucins was investigated in animals receiving carcinogen with or without jejunoileal bypass. (n = 17), as previously described Olubuyide et al., 1984). Animals received Oxoid SGI breeding diet (H.C. Styles and Son, Bewdley, Worcs., UK) and water ad libitum. Quarters were lit with alternate 12 h cycles. Besides being weighed weekly, rats were examined daily for evidence of rectal bleeding and diarrhoea. Moribund animals (n = 10) were sacrificed prematurely and autopsied to ascertain the cause of death. Food and water consumption was measured weekly by cage. Materials and methods FortySurviving animals (n = 32) were killed 30 weeks postoperatively by cervical dislocation after exposure to ether. The entire intestinal tract was removed, freed of fat and adhesions and flushed clean with saline. The length of the duodenum (pylorus to ligament of Treitz) and the large intestine (ileocaecal valve to anus) was measured immediately after suspension of the bowel by a fixed weight (3.9 g) against a vertical scale. These segments of gut were laid flat and opened along the antimesenteric border. The mucosa was scrutinised, and all tumours were recorded, excised and fixed in 10% formalin for subsequent histological and histochemical examination, after which the bowel was mopped dry and weighed. Short segments of non-tumour-bearing bowel were cut from the duodenum (mid-way between pylorus and ligament

“…A large proportion of colonic mucins from normal human colon consists of sulphomucins, whereas in colonic tumours a marked decrease or absence of sulphomucins is accompanied by an increase in sialomucins (Filipe, 1979). However, it has also been found that normal colonic mucosa adjacent to and remote from colon carcinomas show a shift towards sialomucins (Filipe & Branfoot, 1974;Shamsuddin et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Conjugation of 1-naphthol by human colon and tumour tissue using different experimental systems

Gibby¹,

Cohen²

1984

Summary The metabolism of 1-naphthol, a model phenolic substrate, to its glucuronic acid and sulphate ester conjugates has been studied in short-term organ cultures of normal human colon and tumour tissue, subcellular fractions of these tissues, human colonic tumour cell lines and human colonic tumour xenografts. Normal colonic tissue, in short-term organ culture, formed more 1-naphthyl sulphate than glucuronic acid conjugates. In contrast the colonic tumours, under the same conditions, produced more l-naphthyl ,B-Dglucuronide than l-naphthyl sulphate. A marked interindividual variation in sulphate ester and glucuronic acid conjugation was noted in both normal and tumorous colon. The conjugation of 1-naphthol was also investigated, using subcellular fractions, where the metabolism found with normal colon reflected that observed utilizing short-term organ culture, but that from colonic tumour samples did not. Cell lines derived from human colonic adenocarcinomas metabolised l-naphthol almost exclusively to its glucuronic acid conjugate. Xenografts derived from human colonic tumours formed similar conjugates to surgical samples in culture. Thus somewhat different results were obtained dependent on the experimental model chosen. However, in all colonic tumour systems studied, when the cells remained intact and where tissue architecture was maintained, 1-naphthol was metabolised predominantly to its glucuronic acid conjugate.