Ethylene diamine tetraacetic acid-induced colonic crypt cell proliferation in rats.

ABSTRACT

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.