In vivo crypt surface hyperproliferation is decreased by butyrate and increased by deoxycholate in normal rat colon: Associated in vivo effects on c-Fos and c-Jun expression

Omaida C Velazquez, Dongying Zhou, Renée W. Seto, Abdul Jabbar, Julie Choi, Howard M. Lederer, John L. Rombeau

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Background: Studies on colon carcinogenesis suggest that the short- chain fatty acid butyrate may be protective, whereas the secondary bile acid deoxycholate may promote tumor development. Crypt surface hyperproliferation is regarded as a biomarker of colon cancer risk and can be modulated in vitro by the differentiation inducer butyrate and the tumor promoter deoxycholate. We hypothesized that butyrate decreases and deoxycholate increases crypt surface proliferation in vivo and that these effects are mediated by changes in the expression of the protooncogenes c-Fos and c-Jun, which are known to regulate proliferation and differentiation. Methods: Twenty-five adult Sprague-Dawley rats underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L sodium chloride, 10 mmol/L sodium butyrate, or 10 mmol/L sodium deoxycholate. Proliferation of the whole crypt and five crypt compartments from base to surface was assessed by proliferating cell nuclear antigen immunohistochemistry. The φh value, an index of 'premalignant' hyperproliferation, was calculated as the ratio of labeled cells in the two surface compartments divided by the labeled cells in the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot. Results: Crypt surface proliferation and the φh value were significantly decreased by butyrate and increased by deoxycholate. Butyrate increased colonic expression of c-Jun, whereas deoxycholate significantly induced c-Fos. Conclusions: The in vivo effects on surface proliferation are consistent with a potential tumor-promoting role for butyrate and a promotive role for deoxycholate in colon carcinogenesis. The concurrently observed effects on colonic c-Jun and c-Fos expression represent a novel finding and suggest that direct or indirect modulation of protooncogene expression may be the mechanism by which these dietary byproducts regulate proliferation in vivo.

Original languageEnglish
Pages (from-to)243-250
Number of pages8
JournalJournal of Parenteral and Enteral Nutrition
Volume20
Issue number4
StatePublished - Jul 1 1996
Externally publishedYes

Fingerprint

deoxycholic acid
Deoxycholic Acid
Butyrates
butyrates
colon
Colon
rats
proto-oncogenes
carcinogenesis
neoplasms
Carcinogenesis
proliferating cell nuclear antigen
Butyric Acid
Volatile Fatty Acids
Proliferating Cell Nuclear Antigen
bile acids
short chain fatty acids
Bile Acids and Salts
colorectal neoplasms
Sodium Chloride

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

In vivo crypt surface hyperproliferation is decreased by butyrate and increased by deoxycholate in normal rat colon : Associated in vivo effects on c-Fos and c-Jun expression. / Velazquez, Omaida C; Zhou, Dongying; Seto, Renée W.; Jabbar, Abdul; Choi, Julie; Lederer, Howard M.; Rombeau, John L.

In: Journal of Parenteral and Enteral Nutrition, Vol. 20, No. 4, 01.07.1996, p. 243-250.

Research output: Contribution to journalArticle

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abstract = "Background: Studies on colon carcinogenesis suggest that the short- chain fatty acid butyrate may be protective, whereas the secondary bile acid deoxycholate may promote tumor development. Crypt surface hyperproliferation is regarded as a biomarker of colon cancer risk and can be modulated in vitro by the differentiation inducer butyrate and the tumor promoter deoxycholate. We hypothesized that butyrate decreases and deoxycholate increases crypt surface proliferation in vivo and that these effects are mediated by changes in the expression of the protooncogenes c-Fos and c-Jun, which are known to regulate proliferation and differentiation. Methods: Twenty-five adult Sprague-Dawley rats underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L sodium chloride, 10 mmol/L sodium butyrate, or 10 mmol/L sodium deoxycholate. Proliferation of the whole crypt and five crypt compartments from base to surface was assessed by proliferating cell nuclear antigen immunohistochemistry. The φh value, an index of 'premalignant' hyperproliferation, was calculated as the ratio of labeled cells in the two surface compartments divided by the labeled cells in the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot. Results: Crypt surface proliferation and the φh value were significantly decreased by butyrate and increased by deoxycholate. Butyrate increased colonic expression of c-Jun, whereas deoxycholate significantly induced c-Fos. Conclusions: The in vivo effects on surface proliferation are consistent with a potential tumor-promoting role for butyrate and a promotive role for deoxycholate in colon carcinogenesis. The concurrently observed effects on colonic c-Jun and c-Fos expression represent a novel finding and suggest that direct or indirect modulation of protooncogene expression may be the mechanism by which these dietary byproducts regulate proliferation in vivo.",
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T1 - In vivo crypt surface hyperproliferation is decreased by butyrate and increased by deoxycholate in normal rat colon

T2 - Associated in vivo effects on c-Fos and c-Jun expression

AU - Velazquez, Omaida C

AU - Zhou, Dongying

AU - Seto, Renée W.

AU - Jabbar, Abdul

AU - Choi, Julie

AU - Lederer, Howard M.

AU - Rombeau, John L.

PY - 1996/7/1

Y1 - 1996/7/1

N2 - Background: Studies on colon carcinogenesis suggest that the short- chain fatty acid butyrate may be protective, whereas the secondary bile acid deoxycholate may promote tumor development. Crypt surface hyperproliferation is regarded as a biomarker of colon cancer risk and can be modulated in vitro by the differentiation inducer butyrate and the tumor promoter deoxycholate. We hypothesized that butyrate decreases and deoxycholate increases crypt surface proliferation in vivo and that these effects are mediated by changes in the expression of the protooncogenes c-Fos and c-Jun, which are known to regulate proliferation and differentiation. Methods: Twenty-five adult Sprague-Dawley rats underwent colonic isolation and 24-hour intraluminal instillation of 10 mmol/L sodium chloride, 10 mmol/L sodium butyrate, or 10 mmol/L sodium deoxycholate. Proliferation of the whole crypt and five crypt compartments from base to surface was assessed by proliferating cell nuclear antigen immunohistochemistry. The φh value, an index of 'premalignant' hyperproliferation, was calculated as the ratio of labeled cells in the two surface compartments divided by the labeled cells in the entire crypt. Expression of c-Fos and c-Jun was evaluated by Western blot. Results: Crypt surface proliferation and the φh value were significantly decreased by butyrate and increased by deoxycholate. Butyrate increased colonic expression of c-Jun, whereas deoxycholate significantly induced c-Fos. Conclusions: The in vivo effects on surface proliferation are consistent with a potential tumor-promoting role for butyrate and a promotive role for deoxycholate in colon carcinogenesis. The concurrently observed effects on colonic c-Jun and c-Fos expression represent a novel finding and suggest that direct or indirect modulation of protooncogene expression may be the mechanism by which these dietary byproducts regulate proliferation in vivo.

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