Abstract
Objective To investigate the effects of 1,2-dimethylhydrazine (DMH) and estrogen on colonic crypt fission and aberrant crypt foci (ACF) formation.Methods Thirty female 4-months-old Sprague-Dawley rats were divided into five groups.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; and group E was ovariectomized and injected with both DMH and estradiol.The rats were sacrificed after 8 weeks of chemical treatment.The colonic ACF formation,crypt fission,crypt volume and crypt proliferating cell nuclear antigen (PCNA) expression were analyzed.Results The number of total ACF and the ACF with AC (＞6) in group D were larger than group B (57.80 ±6.54 vs.29.67 ±6.15,P ＜0.01,9.00 ±3.16vs.2.83 ±1.33,P＜0.01) and group E (38.40±4.22,P ＜0.01,4.40± 1.34,P ＜0.01).Crypt fission index in group D was larger than group B [ ( 17.60 ± 4.93 ) ％ vs.( 1.50 ± 1.05 ) ％,P ＜0.01 ] and group E [ ( 1.40 ± 0.55 ) ％,P ＜ 0.01 ].The PCNA index in group D was much larger than group A (P＜0.01),group B (P＜0.01),and group C (P＜0.O1),and smaller than group E (P＜0.01 ).The crypt volume was increased exclusively in group D (P ＜ 0.01 ).There was an evident correlation (P ＜ O.05) between the high crypt fission index and high amount of large ACF.The crypt fission was correlated to the crypt volume instead of the crypt cell PCNA expression.Conclusion DMH promoted the ACF formation and development,and also promoted the crypt fission.Ovariectomy alone had no similar effect,but it could exaggerate,while estradiol replacement could inhibit the DMH-induced elevation of crypt fission index and ACF development.These results suggested that the influence on crypt fission might be involved in the carcinogenetic effects of DMH and protective effect of estrogen on rat colon.And the mechanism underlying the crypt fission acceleration might be more complicated than promotion of crypt cell proliferation. Key words: Colon carcinoma; Crypt fission; Estradiol; 1,2-dimethylhydrazine
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