AIM: To investigate the effect of ethylene diamine tetraacetic acid (EDTA) on proliferation of rat colonic cells.

METHODS: EDTA was administered into Wistar rats, carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats was studied with immunohistochemistry.

RESULTS: Marked regional differences in cell proliferation were found in all groups. In EDTA-treated animals, total labelling indexes in both proximal (10.00 ± 0.44 vs 7.20 ± 0.45) and distal (11.05 ± 0.45 vs 8.65 ± 0.34) colon and proliferative zone size (21.67 ± 1.13 vs 16.75 ± 1.45, 27.73 ± 1.46 vs 21.74 ± 1.07) were significantly higher than that in normal controls (P < 0.05) and lower than that in DMH group (10.00 ± 0.44 vs 11.54 ± 0.45, 11.05 ± 0.45 vs 13.13 ± 0.46, 21.67 ± 1.13 vs 35.52 ± 1.58, 27.73 ± 1.46 vs 39.61 ± 1.32, P < 0.05). Cumulative frequency distributions showed a shift of the EDTA distal curve to the right (P < 0.05) while the EDTA proximal curve did not change compared to normal controls. Despite the changes of proliferative parameters, tumours did not develop in EDTA treated animals.

CONCLUSION: Hyperproliferation appears to be more easily induced by EDTA in distal colon than in proximal colon. Hyperproliferation may need to exceed a threshold to develop colonic tumours. EDTA may work as a co-factor in colonic tumorigenesis.

• Adenocarcinoma/chemically induced
• Adenocarcinoma/pathology
• Adenoma/chemically induced
• Adenoma/pathology
• Animals
• Bromodeoxyuridine
• Cell Division/drug effects
• Chelating Agents/pharmacology
• Colon/cytology
• Colon/drug effects
• Colorectal Neoplasms/chemically induced
• Colorectal Neoplasms/pathology
• Disease Models, Animal
• Edetic Acid/pharmacology
• Male
• Rats
• Rats, Wistar

AIM: To investigate the patterns of cell proliferation in proximal and distal colons in normal rats and rats with 1,2-dimethylhydrazine (DMH) induced carcinogenesis using the thymidine analogue bromodeoxyuridine.

METHODS: Colonic crypt cell proliferation was immunohistochemically detected using the anti-bromodeoxyuridine Bu20a monoclonal antibody.

RESULTS: Marked regional differences were found in both groups. Total labelling index (LI) and proliferative zone size in both normal (8.65 ± 0.34 vs 7.2 ± 0.45, 27.74 ± 1.07 vs 16.75 ± 1.45) and DMH groups (13.13 ± 0.46 vs 11.55 ± 0.45, 39.60 ± 1.32 vs 35.52 ± 1.58) were significantly higher in distal than in proximal colon (P < 0.05), although the number of cells per proximal crypt was greater (31.45 ± 0.20 vs 34.45 ± 0.39, 42.68 ± 0.53 vs 49.09 ± 0.65, P < 0.0001). Crypt length, total LI and proliferative zone size all increased in both proximal and distal regions of DMH rats compared to normal controls (P < 0.0001). In DMH-treated rat colon a shift of labelled cells to higher crypt cell positions was demonstrated distally whilst a bi-directional shift was evident proximally (P < 0.05).

CONCLUSION: Our results show that changes in cell proliferation patterns, as assessed by bromodeoxyuridine uptake, can act as a reliable intermediate marker of colonic cancer formation. Observed differences between proliferation patterns in distal and proximal colon may be associated with the higher incidence of tumors in the distal colon.

• Animals
• Antimetabolites
• Biomarkers, Tumor
• Bromodeoxyuridine
• Carcinogens
• Cell Division
• Colon/pathology
• Colonic Neoplasms/chemically induced
• Colonic Neoplasms/pathology
• Dimethylhydrazines
• Male
• Rats
• Rats, Wistar