Crypt Proliferation

Cahill, R.J., O Sullivan, K.R, Mathias, P.M., Beattie, S., Hamilton, H. and O Morain, C. (1992). The effect of nutrient antioxidants on colonic crypt cell proliferation in patients with adenomatous polyps. Gastroenterology 102, A919. 

The nucleosides are converted back to nucleosides is reactions known as salvage pathways (Chapter 20). RNA supplements in the diet are also hydrolysed to form nucleosides, which can be taken up by cells in the body to form nucleotides. Although proliferating cells can synthesise nucleotides de novo, provision of nucleosides bypasses a considerable amount of biochemistry. This is important, for example, in lymph nodes for proliferating immune cells in the bone marrow and also for stem cells in the crypts of the villi (Chapter 20). 

The amonnt of protein synthesised and then released in (iv) and (v) is abont 70 g each day. Even under conditions of starvation or malnutrition, proliferation and differentiation of stem cells located in the crypts of the villi are important to provide the cells necessary for replenishment of those lost from the villi. New cells move up the villus to replace those lost at the top. Under these conditions, amino acids are not available from the intestine and have to be taken up from the blood across the basolateral membrane. A low level of amino acids in the blood, due to chronic malnutrition, will prevent or reduce the rate of proliferation of these cells, so that digestion of even the small amount of food ingested during malnutrition, or refeeding after starvation, is difficult. A vicious circle thus results from protein-deficient diets which increase the risk of development of protein-energy-malnutrition. This is especially severe in children but may also contribute to the clinical problems that occur in the elderly whose diets are of low quality. 

Systemic administration of colonic carcinogois yields the entire spectrum of changes seen in human colon cancer, including abnormal crypt architecture with disrupted proliferation, papillary and adenomatous polyps, carcinoma in situ, and adenocarcinoma (Thumherr et al., 1973). The distal colon is affected with the greatest frequency, and squamous cell canc of the anus is also produced. Dietary fat enhances the production of colonic tumors (Nigro et al., 1975), perhaps by increasing bile flow (Narisawa et al., 1974). 

FIGURE 4.1. Effect of antibody (PC 10) concentration on the immunostaining of PCNA antigen in rectal mucosal proliferating cells. (A) The antibody was used at a concentration of 1 100. (B) The antibody was used at a concentration of 1 400. Note the increased labeling, especially in the upper crypt, when antibody concentration of 1 100 was used. Arrows indicate the upper limit of labeled cells. Reproduced, with permission, from Holt et al. (1997). Copyright 1997 American Association for Cancer Research. 

Schmelz, E.M., Sullards, M.C., Dillehay, D.L., Merrill, A.H., Jr. 2000. Colonic cell proliferation and aberrant crypt foci formation are inhibited by dairy glycosphingolipids in 1,2-dimethyl-hydrazine-treated CF1 mice. J. Nutr. 130, 522-527. 

Cell proliferation Histology Aberrant crypt foci (colon polyps precursors)... 

Most dietary folate is reduced and methylated to methyl-tetrahydro-folate in the intestinal mucosa (Section 10.2.1). Intestinal mucosal ceUs have a rapid turnover, typicaUy 48 hours from proliferation in the crypt to shedding at the tip of the vUlus. This means that an unstable variant of the enzyme, which loses activity over a shorter time than the normal enzyme, is probably irrelevant in ceUs that have such a rapid turnover. A high intake of folate would therefore result in a relatively high rate of supply of methyl-tetrahydrofolate to cells, arising from newly absorbed folate, so that impaired turnover of folate within cells would be less important. 

Altmann GG, Lala PK. 1991. Control of 1,2-dimethylhydrazine-induccd crypt hyperplasia by natural-killer cells and its relevance to carcinogenics. In Chemically induced cell proliferation Implications for risk assessment. New York, NY Wiley-Liss, Inc. 417-428. 

Perineurioma of the GI tract is a relatively recently described entity that rarely presents as a polypoid lesion. These lesions are composed of a bland spindle cell proliferation with delicate cytoplasmic protrusions that emanate from either side of an elongated nucleus. Like neurofibroma, this lesion grows around and entraps adjacent intestinal crypts. Analogous to perineuriomas of the soft tissues, intestinal perineuriomas almost uniformly stain with epithelial membrane antigen (EMA) a subset of these lesions expresses claudin-1. These lesions are negative for smooth muscle markers, S-100 protein, and c-kit. 

Whether Wnt-RA synergy is observed in other lineages is presently unknown. However, it is interesting to note that RA increases crypt formation and proliferation in intestinal grafts, and that this effect is paralleled by an induction of Cdxl (Plateroti et al., 1997). As Cdxl is also regulated by TCF4 in the intestine (Lickert et al., 2000, 2001), it is tempting to speculate that retinoid and Wnt... 

In another study, Santana-Rios et al. ° found 5.65 0.81 and 1.31 0.27 aberrant crypt foci (ACF) per colon in groups of rats given 2-amino-l-methyl-6-phenylimid-azo[4,5-b]pyridine (PhIP) and PhIP+white tea, respectively, during 8 weeks of study. White tea also inhibited cell proliferation and suppressed early lesions in the colon. ... 

The roles of sphingolipids in chemoprevention have also been reported previously (Borek and Merrill, 1993). Administration of SM in the diet prevents the formation of chemically induced colon cancer tumors and aberrant colonic crypts by decreasing the rate of cell proliferation and increasing apoptosis in mice (Schmelz et ah, 1996). Diets supplemented with ceramide, SM, glucosyl-ceramide, lactosylceramide, or ganglioside GD3 to C57B1/6 J(Min/ + ) mice with a truncated APC gene product, reduced the number of tumors in the intestine (Schmelz et al., 1996, 2000). 

Ochiai M, Watanabe M, Kushida H, Wakabayashi K, Sugimura T, Nagao M. DNA adduct formation, cell proliferation and aberrant crypt focus formation induced by PhIP in male and female rat colon with relevance to carcinogenesis. Carcinogenesis 1996 17 95-98. 

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