Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.

Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides

Vitamin D deficiency : a worldwide problem with health consequences

Molecular and cellular mechanisms of cadmium carcinogenesis

Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix Nancy Boudreau,* Carolyn J. Sympson, Zena Werb, Mina J. Bissell N. Boudreau and M. J. Bissell Life Sciences Division, Lawrence Berkeley Laboratory 1 Cyclotron Road, Building 83, Berkeley, CA 94720, USA. C. J. Sympson Life Sciences Division, Lawrence Berkeley Laboratory 1 Cyclotron Road, Building 83, Berkeley, CA 94720, USA Laboratory of Radiobiology and Environmental Health University of California, San Francisco, CA 94143, USA. Z. Werb Laboratory of Radiobiology and Environmental Health University of California, San Francisco, CA 94143, USA. *To whom correspondence should be addressed. LBNL/DOE funding & contract number: DE-AC02-05CH11231 DISCLAIMER This document was prepared as an account of work sponsored by the United States Government. While this document is believed to contain correct information, neither the United States Government nor any agency thereof, nor The Regents of the University of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or The Regents of the University of California. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof or The Regents of the University of California.

Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix

Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.

The role of vitamin D in reducing cancer risk and progression

Convincing evidence is available showing that dietary calcium and vitamin D impede the development of colonic carcinogenesis. The major cellular modes of action of calcium and vitamin D which can contribute to the inhibition of colonic neoplasia are reviewed in this article. These consist of complex series of signaling events induced by the chemopreventive agents acting at various tiers of colonic cell organization.

Cellular Mechanisms of Calcium and Vitamin D in the Inhibition of Colorectal Carcinogenesis

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

The intriguing observation has been made that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptors are present in tissues not involved in calcium homeostasis and that 1,25(OH)2D3 exerts an antiproliferative, differentiation-promoting action in a variety of cancer cell lines, including cells of the large intestine. It was therefore deemed of interest to study 1,25(OH)2D3 expression and biological activity in a murine model of colon carcinogenesis. Colon carcinogenesis was induced in male rats by the sequential administration of 1,2-dimethylhydrazine dihydrochloride (DMH). Levels and binding characteristics of 1,25(OH)2D3 receptors were assessed in control and DMH-treated rat colonic mucosal high-speed supernatants. In concurrent studies, 1,25(OH)2D3 was administered (s.c., 400 ng/rat) prior to, together with and after DMH challenge and the activity of ornithine decarboxylase (ODC), a growth-related DMH-induced enzyme, was determined in colonic cytosols. Serum Ca2+ levels were measured concurrently. Rats submitted to identical treatment schedules were killed 10 weeks after termination of DMH administration and the whole colon was opened and examined for tumors. The results show that (i) rat colonic mucosa possesses a single class of high-affinity 1,25(OH)2D3 receptors; (ii) DMH administration provokes a marked reduction (50%) in 1,25(OH)2D3 binding sites without affecting Kd values; (iii) DMH administered concurrently with 1,25(OH)2D3 suppressed the vitamin D-induced hypercalcemia and restored serum Ca2+ concentrations to basal levels; and (iv) 1,25(OH)2D3 delivered prior to DMH challenge obliterated the typical DMH-induced early colonic ODC activity peak and markedly reduced (50%) the number of colon adenocarcinomas. The present findings indicate that a colon-specific potent carcinogen interferes with the biological expression of 1,25(OH)2D3 and that vitamin D administered prior to a carcinogenic insult is able to reduce significantly the incidence of colon tumors, presumably acting as an antiproliferative or differentiation-promoting agent.

A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis

It is widely believed that stem cells are the relevant target cells for colonic cell transformation. Evidence is presented that a proliferative transit daughter cell acquiring a mutant adenomatous polyposis coli gene during upward migration from the crypt base can develop retention abnormalities and permanence in the crypt, thus qualifying as a transformed clone which is retained in the colonic epithelium.

/pdf/migrating-colonic-crypt-epithelial-cells-primary-targets-for-43gx1zbpen.pdf

Migrating colonic crypt epithelial cells: primary targets for transformation.

The aim of the present work was to gain insight into a putative anticancer effect of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis. Male rats were assigned to three different dietary groups. The dietary regimens were based on a standard murine-defined diet (AIN-76A) or a stress diet containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio, and either low or high vitamin D3 content. Colorectal cancer was induced by administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ], and 25-hydroxyvitamin D3 [25(OH)D3 ] levels were measured in DMH-treated rats and in respective weight- and age-matched dietary control groups. Colonic epithelial proliferation was assessed by determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd) incorporation into crypt cell DNA, and the mean labeling index along the colonic crypt continuum. Maintenance of rats on the stress diet either unmodified or suppleme...

Lamprecht Sa

Papers

Cellular Mechanisms of Calcium and Vitamin D in the Inhibition of Colorectal Carcinogenesis

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis

Migrating colonic crypt epithelial cells: primary targets for transformation.

A protective role of dietary vitamin D3 in rat colon carcinogenesis.