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. 2000 Nov;47(5):632–637. doi: 10.1136/gut.47.5.632

Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans

D Keefe 1, J Brealey 1, G Goland 1, A Cummins 1
PMCID: PMC1728102  PMID: 11034578

Abstract

BACKGROUND AND AIMS—The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans.
METHODS—Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique.
RESULTS—Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days.
CONCLUSION—Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height.


Keywords: chemotherapy; mucositis; small intestine

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Figure 1  .

Figure 1  

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Changes in intestinal morphology before (A) and at three days after (B) chemotherapy for cancer. (Original magnification ×156.)

Figure 2  .

Figure 2  

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Changes in villus area and crypt length before (Pre) and after chemotherapy for cancer. Data are given as mean (SEM).

Figure 3  .

Figure 3  

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Changes in mitotic count per crypt (A) and apoptotic count per crypt per 4 µm section (B) before (Pre) and after chemotherapy for cancer. Data are given as mean (SEM).

Figure 4  .

Figure 4  

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Light photomicrograph showing two apoptotic cells (arrows) in the crypt of the small intestine at one day after chemotherapy. Apoptosis was detected using the TUNEL technique. (Original magnification ×292.)

Figure 5  .

Figure 5  

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Electron micrograph of an apoptotic cell in the epithelial layer of the small intestinal crypt at one day after chemotherapy. The arrow indicates an apoptotic cell with a pyknotic nucleus. (Original magnification ×12 000.)

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