The Effect Of Estrogen And 1, 2-dimethylhydrazine On Crypt Fission Of Rat Colon

Objectives:To investigate the effects of estrogen and 1,2-dimethylhydrazine(DMH) on colonic crypt fission and aberrant crypt foci(ACF) formation.Methods: Thirty female 4-months-old Sprague-Dawley rats were divided into five groups, six in each group. Group A was the blank control, which was treated with vehicle injection after a sham operation; group B was treated with DMH after sham operation; group C was ovariectomized and treated with vehicle injection, group D was ovariectomized and treated with DMH injection, group E was ovariectomized and injected with both DMH and estrogen. The operations were performed at the beginning of the experiment, and then chemical treatment began 1 week thereafter. DMH(25mg/Kg, weekly, 8 weeks) was injected by intraperitoneal route, and 17β-estradiol (250μg/Kg, weekly, 10 weeks) was injected subcutaneously. Normal saline and sesame oil were vehicles of DMH and estradiol respectively. The rats were sacrificed 12 weeks after the operation. The colonic ACF formation, crypt fission , crypt volume and crypt proliferation status were analyzed.. Results: No dividing crypt or ACF was observed in group A and C , both groups were treated without DMH. Crypt fission index in group D was larger than group B ( 17.60±4.93vs1.50±1.05%, P<0.001 ) and E(17.60±4.93vs1.40±0.55%, P<0.001). The total number of ACF and the number of ACF with AC(>6) in group D were larger than group B ( 57.80±6.54vs29.67±6.15 , P<0.001, 9.00±3.16vs2.83±1.33, P<0.001 ) and E ( 57.80±6.54vs38.40±4.22 , P<0.001, 9.00±3.16vs4.40±1.34, P<0.001). The PCNA index in group D was much larger than group A(P<0.001), B(P<0.001), and C(P<0.001) and smaller than group E(P<0.001). The crypt volume increased exclusively in group D (P<0.001). There was an evident correlations (P<0.05) between the high crypt fission index and high amount of large ACF ..Conclusion: DMH promoted crypt fission, while ovariectomy alone did not. However, ovariectomy could exaggerate while estrogen replacement inhibit the DMH induced elevation of crypt fission index. Crypt fission maybe correlated with the crypt volume but not with crypt proliferation. In addition, high crypt fission index may implicate the high risk of colon neoplasma because of a higher amount of large ACF.