A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowel

Potten, Christopher S; Li, Y Q; O’Connor, Peter J.; Winton, Douglas J.

doi:10.1093/carcin/13.12.2305

Cited by 136 publications

(68 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the distribution of the M chain primarly at the bottom of the crypts in human does not support this hypothesis, since in small intestine the proliferative cells are located higher in the cell columns, above the Paneth cells (Potten and Loeffler, 1987;Potten et al, 1992). Perhaps M-laminin is in- Fig.…”

Section: Discussionmentioning

confidence: 96%

Differential expression of laminin isoforms and α6‐β4 integrin subunits in the developing human and mouse intestine

Simon‐Assmann¹,

Duclos²,

Orian-Rousseau³

et al. 1994

Developmental Dynamics

107

View full text Add to dashboard Cite

The intestinal tissue is characterized by important morphogenetic movements during development as well as by a continuous dynamic crypt to villus epithelial cell migration leading to differentiation of specialized cells. In this study, we have examined the spatio-temporal distribution of laminin A and M chains as well as of a6 and p4 integrin subunits in adult and developing human and mouse intestine by indirect immunofluorescence. Selective expression of the constituent polypeptides of laminin isoforms (A and M chains) was demonstrated. In the mature human intestine, A and M chains were found to be complementary, the M chain being restricted to the base of crypts and the A chain lining the villus basement membrane. In the developing human intestine, M chain expression was delayed as compared to that of A chain; as soon as the M chain was visualized, it exhibited the typical localization in the crypt basement membrane. A somewhat different situation was found in the adult mouse intestine, since both M and A chains were found in the crypts. During mouse intestinal development the delayed expression of the M chain as compared to that of the A chain was also obvious. The absence of M chain expression in mutant dy mouse did not impair intestinal morphogenesis nor cell differentiation. The expression of a6 and p4 subunits was not coordinated. In both species the a6 expression preceded that of p4. Furthermore, while p4 staining in adult mouse intestine was detected at the basal surface of all cells lining the cryptvillus, that of a6 was mainly confined to the crypt cell compartment. An overall similarity of location between a6 integrin subunit and laminin A chain at the epithelial/stromal interface was noted. These data indicate that the spatial and temporal distribution of laminin variants in the developing intestine may be characteristic for each species and that interactions of laminin variants with particular receptors may be important for induction and/or maintenance of differentiated cells.

show abstract

Section: Discussionmentioning

confidence: 96%

Differential expression of laminin isoforms and α6‐β4 integrin subunits in the developing human and mouse intestine

Simon‐Assmann¹,

Duclos²,

Orian-Rousseau³

et al. 1994

Developmental Dynamics

107

View full text Add to dashboard Cite

show abstract

“…In addition to alterations at the individual crypt level, the colonic mucosa has been shown to alter its growth characteristics by crypt duplication, increasing the number of crypts per unit length and increasing its total length in response to alterations in diet (1, 19, 22, 29, suggests that differences in the rate at which crypt epithelial cells enter the process of apoptosis is the reason for the marked disparity in incidence of neoplasia in the colon and small intestine, despite the very high rate of cell replication [turnover of the entire mucosa every 3-6 days (22)] at both sites (39). Clearly, there is a need to gain a better understanding of methods used to measure mucosal growth in the colon, the role of bacterial metabolites in mucosal growth, and the relationship of these factors to colonic mucosal pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

et al. 1996

View full text Add to dashboard Cite

The colonic mucosa can adapt its growth to alterations in diet. Metabolites from colonic microflora are frequently implicated as the primary factor in mediating the colonic mucosal response to diet; however, there is also evidence indicating that diet may have a direct effect in mediating this response. The aim of this study was to determine the role of diet, microflora, and microflora metabolites in altering the growth of the colonic mucosa. Two 28-day feeding studies were conducted using Sprague-Dawley rats. The first study compared the growth of the colonic mucosa in germ-free and conventional rats fed 6 different diets. The second study compared the growth of the colonic mucosa to the concentration of bacterial-derived short-chain fatty acids (SCFAs), bile acids, and ammonia. The diets that were fed consisted of (1) AIN-76a diet without dietary fiber; (2) standard AIN-76a diet, which contained 5% cellulose; (3) AIN-76a diet with 5% guar gum; (4) a "Western" human diet with 20% fat and 10% cellulose; (5) AIN-76a diet formulated to mimic Diet 4 in fat content but with 2.5% cellulose; and (6) Purina Rodent Chow. Quantitative volumetric and stereologic analysis was used to assess changes in total colonic mucosal volume as a measure of mucosal growth. In germ-free rats, Diets 2-4 and 6 induced a significant increase (18-38%) in mucosal volume compared to Diet 1. In conventional animals, only Diets 4 and 6 induced a significant increase (up to 63%) in mucosal volume compared to Diet 1. Relative to the germ-free animals, only conventional animals on Diets 4 and 6 had an increase in mucosal volume. The increases in mucosal volume in Diets 4 and 6 were not consistently associated with increased SCFAs, ammonia, or bile acids. There was a wide range in the colonic concentrations of SCFAs (2-fold), ammonia (6-fold), and bile acids (10-fold). The presence of colonic microflora in and of itself does not lead to enhanced colonic mucosal growth. Rather, there are unique interactions between specific types of diet and microflora that lead to a growth-promoting effect. This effect could not be explained by alterations in the concentration of SCFAs, ammonia, or bile acids in colonic contents.

show abstract

“…In contrast to the prostate and seminal vesicles, the proliferation rate in the small bowel is higher than in large bowel, whereas the cancer incidence is higher in large bowel. 27 Our study demonstrated that the cell turnover in normal seminal vesicles is lower than in the prostate and therefore there is no evidence of an increased apoptotic rate as the reason for the extremely low cancer incidence of the seminal vesicles.…”

Section: Discussionmentioning

confidence: 51%

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

Pannek

Berges

Sauvageot³

et al. 1999

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

The human prostate and seminal vesicles are both androgen-dependent sex accessory organs. Their growth behavior, response to hormone manipulation, susceptibility to benign and malignant processes and sex accessory functions, however, differ greatly. The growth behavior of most tissues correlates well with the cell turnover rate of that tissue. Therefore, we compared the cell turnover of normal human prostate and seminal vesicles.Immunohistochemical expression of MIB-1 (proliferation), bcl-2 and transforming growth factor (TGF b) were examined in 20 different samples taken from histologically normal human prostatic and seminal vesicle tissue. For the quanti®cation of apoptosis, the TUNEL technique was used.The apoptosis rates in normal prostatic tissue (0.73 AE 0.60) were signi®cantly greater (P 0.003) than those seen in seminal vesicles (0.02 AE 0.01). The proliferation rates also differed signi®cantly (P 0.002) between these tissues (prostate: 0.77 AE 0.78; seminal vesicles: 0.02 AE 0.02). Eighty percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the prostate samples stained for TGF b b. For both androgen-dependent tissues, apoptotic rates closely equaled proliferation rates. The cell turnover, however, was much higher in the prostate than in the seminal vesicles. TGF b seems to be more important for the regulation of cell turnover in the seminal vesicles than bcl-2. These differences in the proliferative behavior may explain why disturbances of apoptotic regulation lead to a more extensive net cell gain in prostatic tissue compared to the seminal vesicles. This might help explain the vastly different incidence of benign and malignant tumors in these organs.

show abstract

A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowel

Cited by 136 publications

References 0 publications

Differential expression of laminin isoforms and α6‐β4 integrin subunits in the developing human and mouse intestine

Differential expression of laminin isoforms and α6‐β4 integrin subunits in the developing human and mouse intestine

The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

Contact Info

Product

Resources

About