BMC Cancer 2009, 9:251 http://www.biomedcentral.com/1471-2407/9/251 TFhigeudrieffe2rences in the measured crypt length were significant before and after treatment by azoxymethane The differences in the measured crypt length were significant before and after treatment by azoxymethane. CyCAP-/- animals spontaneously developed increased crypt length and also developed much more exuberant response to azoxymethane treatment (A), which resulted in more hyperplasia (A) larger number of adenomas (p = 0.003, Linear Regres- sion) (B) and increased cumulative size of adenomas (p = 0.016, Linear Regression) (C). The CyCAP-/- untreated animals also spontaneously developed higher crypt proliferation ratio (p = 0.039, Mann-Whitney Test) (D). nounced mucosal hyperplasia suggesting that colorectal hyperplasia in our model is a preneoplastic change. In mice, colonic mucosal hyperplasia can be caused by infection. Transmissible murine colonic hyperplasia is the only naturally occurring hyperplastic disease of the colon in mice [65]. This severe but transient mucosal hyperpla- sia of the distal colon is caused by Citrobacter freundii [48] and was shown to have an expansion of the proliferative zone, an increased labeling index, a prolongation of the cell cycle time, an increase in variation of DNA synthesis times resulting in prolongation of the S phase, and an accelerated migration rate [66]. Interestingly, these find- ings parallel the "atypical" kinetics found in human and murine preneoplastic and neoplastic disorders of the colon, and also abnormal proliferative kinetics which occur in the flat mucosa of humans between existing tumors or polyps and in the preneoplastic mucosa of rodents treated with carcinogens [60,62]. Hyperplasia, analogous to tumor promoters which induce proliferation Page 6 of 11 (page number not for citation purposes)