Apoptosis (programmed cell death) in colonic cells : from normal to transformed stage

• Published in: Cancer letters Vol. 163; no. 2; pp. 229 - 238
• Main Authors: LIFSHITZ, Sarit, LAMPRECHT, Sergio A, BENHARROCH, Daniel, PRINSLOO, Isebrand, POLAK-CHARCON, Sylvie, SCHWARTZ, Betty
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 26-02-2001
• Subjects: 1,2-Dimethylhydrazine; Ageing, cell death; Animal tumors. Experimental tumors; Animals; Apoptosis; Biological and medical sciences; Biomarkers - analysis; Carcinogens; Caspase 1 - analysis; Cell physiology; Cell Transformation, Neoplastic - metabolism; Colon - cytology; Colonic Neoplasms - chemically induced; Colonic Neoplasms - pathology; Colonic Neoplasms - physiopathology; Experimental digestive system and abdominal tumors; Fundamental and applied biological sciences. Psychology; In Situ Nick-End Labeling; Male; Medical sciences; Molecular and cellular biology; Precancerous Conditions - chemically induced; Precancerous Conditions - pathology; Precancerous Conditions - physiopathology; Rats; Tumors; Rat; Gene product; Cysteine endopeptidases; Tumoral tissue; Cell transformation; Carcinogenesis; Fragmentation; Malignant transformation; Tumor progression; Intestinal disease; Colon; Tumor cell; Premalignant lesion; Enzyme; Rodentia; Malignant tumor; Gene expression; In vitro; Colonic disease; Peptidases; Vertebrata; Mammalia; Interleukin 1-β converting enzyme; Cell death; Animal; DNA; Digestive diseases; Hydrolases; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(00)00624-8

We determined apoptosis in whole rat colonic tissue and in isolated colonocytes from the various rat crypt regions in preneoplastic stages up to frank neoplasia following administration of the procarcinogen, dimethylhydrazine (DMH). Apoptotic cells were determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)-method, by evaluating sections stained with hematoxylin and eosin, and caspase-1 immunostaining. Apoptotic cells in whole colonic tissue from untreated rats were confined to the upper crypt while, in DMH-treated rats apoptotic and caspase-1 positive cells were located in the crypt proliferative regions. Numerous apoptotic and caspase-1-positive cells were found in sections from early tumors while in the delayed tumors, apoptotic-positive cells were absent and number of caspase-1-positive cells was negligible. A marked reduction in the apoptotic index along the crypt was observed in isolated transformed colonic cells, this was not the case for caspase-1-positive cells. We conclude that: (i) in colorectal tumors at progressive stage apoptosis is altered, (ii) the mechanistic alteration in apoptosis may be located between caspase-1-protease activity and the fragmentation process of DNA.