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. 2001 Sep;49(3):418–422. doi: 10.1136/gut.49.3.418

Increased rectal cell proliferation following alcohol abuse

U Simanowski 1, N Homann 1, M Knuhl 1, L Arce 1, R Waldherr 1, C Conradt 1, F Bosch 1, H Seitz 1
PMCID: PMC1728428  PMID: 11511565

Abstract

BACKGROUND—Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers.
METHODS—Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53.
RESULTS—Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis.
CONCLUSION—Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.


Keywords: colorectal cancer; alcohol; rectal mucosa

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Figure 1  .

Figure 1  

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Typical staining patterns of proliferative cell nuclear antigen in nuclei of rectal crypts of controls (A) and alcohol abusers (B) (magnification ×100).

Figure 2  .

Figure 2  

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Proliferative indices (PI) in alcohol abusers and controls, expressed as a percentage of proliferative cell nuclear antigen positive cells in a rectal crypt, subdivided into equal crypt cell compartments, with compartment 1 being at the crypt base and compartment 5 adjacent to the crypt-luminar junction.

Figure 3  .

Figure 3  

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Graphically estimated proliferative compartment (PC) size, expressed as the number of crypt cell compartments, in alcohol abusers and controls. The limit of PC is 50% of the peak proliferative index (PI).

Figure 4  .

Figure 4  

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Staining for Ki67 in rectal crypts of controls (A) and alcohol abusers (B) (magnification ×100).

Figure 5  .

Figure 5  

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Histone H3 mRNA analysed by in situ hybridisation in rectal crypts of controls (A, B) and alcohol abusers (C, D). (B) and (D) are dark field photomicrographs of (A) and (C), respectively. There was considerably increased H3 mRNA in the proliferative regions of rectal crypts of alcoholic subjects (magnification ×80).

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