Variability of cell proliferation in the proximal and distal colon of normal rats and rats with dimethylhydrazine induced carcinogenesis

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 +/- 039, 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.