Adaptation and carcinogenesis in defunctioned rat colon: Divergent effects of faeces and bile acids

Rainey, J. B.; Davies, PamelaA.; Bristol, James; Williamson, R. C. N.

doi:10.1038/bjc.1983.220

Cited by 24 publications

(10 citation statements)

References 17 publications

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“…In the large intestine and to a lesser extent in the small bowel and stomach, we and other have shown that dietary or surgical manipulations causing increased cell proliferation will generally enhance experimental carcinogenesis, whereas atrophy has a protective effect (Oscarson et al, 1979;Rainey et al, 1983;Williamson & Rainey, 1984;Houghton et al, 1987). The present review examines the hypothesis that hyperplasia and neoplasia are similarly linked in the exocrine pancreas.…”

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confidence: 99%

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

Watanapa

Williamson²

1993

Br J Cancer

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Summary Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia.

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confidence: 99%

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

Watanapa

Williamson²

1993

Br J Cancer

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“…Shortly after this experiment was concluded, a very similar study was published which might have predicted these results. Rainey et a1 evaluated local effects of saline, deoxycholic acid, and dilute feces on experimental carcinogenesis in excluded colon segments [21]. Daily instillation of 0.12 M Na deoxycholate (5 ml) failed to influence excluded colon segment tumor incidence or multiplicity when compared to saline irrigated and non-irrigated controls.…”

Section: Discussionmentioning

confidence: 98%

Effects of sodium cholate on experimental carcinogenesis and cell proliferation in an excluded colonic segment

Tempero

Zetterman

1987

Journal of Surgical Oncology

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Bile salts appear to be important promoters of colon carcinogenesis. This study was designed to assess the importance of the fecal stream in cholic acid-induced colon tumor promotion. Male Sprague-Dawley rats underwent transverse colostomy after induction with dimethylhydrazine (DMH) and the excluded distal colon was irrigated with saline or sodium cholate (23 microM) 5 times per week until sacrifice. Controls initially injected with saline were similarly treated. All surviving animals were sacrificed at 28 weeks after the last DMH injection. Five animals from each group were randomly chosen to assess tritiated thymidine labeling and distribution by autoradiography in normal appearing colon mucosa of irrigated bowel. Cholate irrigation failed to increase tumor yield or modify the proportion of adenomas and adenocarcinomas in this model. Paradoxically, fewer tumors per affected rat were noted with sodium cholate irrigation. Cholate irrigation also failed to affect crypt cellularity, thymidine labeling indices, and labeling distribution in DMH-treated rats and controls. An effect of DMH was seen, however, with an increase in thymidine labeling index and increased labeling in the top half of the crypt in all DMH-treated groups. This study suggests that tumor promotion with primary bile salts is not a direct affect and may result from further bile salt metabolism within the fecal stream. DMH-induced changes in cell proliferation were reproduced with this model. Use of an excluded colon segment to assess the effect of suspected tumor promoters on carcinogenesis or colon mucosal cell proliferation is feasible and may be a useful model for future studies.

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“…Certainly, the chronic inflammation of ulcerative colitis in man increases the risk of colorectal cancer (Lennard-Jones et al, 1977;van Heerden & Beart, 1980). We have recently found that isolating a long segment of colon from the faecal stream as a ThiryVella fistula produces both mucosal hypoplasia and reduced susceptibility to azoxymethane (Rainey et al, 1983). SDC instillation into this defunctioned colon has no effect on the reduced tumour yield or the mucosal hypoplasia.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, 3 rats developed tumours of the external auditory canal, and metastases were found in the lung, liver and omentum. Histological types of benign and malignant neoplasms were as previously described (Williamson et al, 1979;Rainey et al, 1983).…”

Section: Experimental Animalsmentioning

confidence: 99%

“…In the rat diversion of pancreaticobiliary secretions to mid small bowel enhances colorectal carcinogenesis (Chomchai et al, 1974;Williamson et al, 1979) and also stimulates marked adaptive hyperplasia of the ileum and moderate colonic hyperplasia (Williamson et al, 1978). However, bile acids appear to be neither tropic nor cocarcinogenic to hypoplastic defunctioned colon (Rainey et al, 1983). The composition of the colonic microbial flora is implicated as the key intermediary modulating the effect of luminal bile acids (Aries et al, 1969;Hill, 1979).…”

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confidence: 99%

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The cocarcinogenic effect of intrarectal deoxycholate in rats is reduced by oral metronidazole

Rainey¹,

Maeda²,

Williams³

et al. 1984

Br J Cancer

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Summary Bile acids enhance colorectal carcinogenesis in animals and man, perhaps after degradation by faecal anaerobes. The promotional effect of sodium deoxycholate (SDC) and its relationship to bacteria was examined in male Sprague-Dawley rats (n = 115) which had received a 6-week course of azoxymethane (total dose 90mg kg 1 s.c.) Two groups received 3 x weekly intrarectal (i.r.) instillations of N saline or 0.12 M SDC for 18 weeks. Another group received SDC i.r. plus metronidazole (22.5mgkg-1) daily in the drinking water. Controls had no instillations or metronidazole alone. By 28 weeks SDC had increased mean colonic crypt depth by 9% (P<0.001), and had almost trebled colorectal tumour yields from 2.4+0.4 per rat (mean + s.e.) in controls to 6.4+0.5 (P<0.001). Tumour yields after SDC + metronidazole (4.2+0.5) remained 75% higher than in controls (P<0.01) but were 33% less than after SDC alone (P<0.01), and the increase in crypt depth was maintained at 7% (P<0.001). Neither metronidazole alone nor saline i.r. had any effect on tumour yield, but metronidazole alone reduced crypt depth by 9% (P<0.001). Deoxycholate is a potent cocarcinogen and also stimulates mucosal hyperplasia. Metronidazole reduces its tumour-promoting effect, suggesting that faecal anaerobes are important in bile acid cocarcinogenesis.

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Adaptation and carcinogenesis in defunctioned rat colon: Divergent effects of faeces and bile acids

Cited by 24 publications

References 17 publications

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

Effects of sodium cholate on experimental carcinogenesis and cell proliferation in an excluded colonic segment

The cocarcinogenic effect of intrarectal deoxycholate in rats is reduced by oral metronidazole

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