A proteomics approach to identify changes in protein profiles in pre-cancerous colon q Janice E. Drew a, * , Garry J. Rucklidge b , Gary Duncan b , Awni Lufty c , Andrew J. Farquharson a , Martin D. Reid b , Wendy R. Russell a , Philip C. Morrice a , John R. Arthur a , Garry G. Duthie a a Cellular Integrity Division, Rowett Research Institute, Greenburn Road, Bucksburn, ABERDEEN, AB21 9SB Scotland, UK b Proteomics Unit, Rowett Research Institute, Greenburn Road, Bucksburn, ABERDEEN, AB21 9SB Scotland, UK c Dumfries Royal Infirmary, Dumfries, Scotland, UK Received 16 February 2005 Abstract The development of colon cancer is characterised by alterations in multiple genetic and epigenetic pathways in colon tissue lead- ing ultimately to deregulation of colon epithelial cells. Early detection is an important factor in decreasing colon cancer deaths. Pro- teomic techniques were used to identify potential early markers in colon tissue exhibiting pre-cancerous activity that may characterise pathological changes in a chemically induced colon cancer rat model. Protein profiles were assessed in soluble and insol- uble fractions prepared from distal colon of rats treated with the colonotropic carcinogen, dimethylhydrazine. Alterations in protein profiles were associated with the presence of aberrant crypt foci, hyperplasia and dysplasia, microanatomical changes, and metabolic changes in rat colon. These changes may have a potential role in the identification of pre-pathological features preceding colon tumorigenesis. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Proteomics; Colon cancer; Rat; Aberrant crypt foci; Prostaglandin Colorectal cancer is the third most common cancer worldwide (excluding skin cancer) after lung and breast cancer [1]. Early detection significantly increases the chances of long-term survival [2]. However, bowel can- cer is often detected at later stages when metastatic can- cers have already progressed. Pathogenesis of colorectal cancer remains poorly understood. Although hereditary links to colorectal cancer development are well estab- lished, the majority of cases are sporadic with little or no evidence of hereditary factors [3]. The identification of novel markers that may predict the onset of pro-can- cerous changes that predispose the colon to increased risk of tumorigenesis will be essential in reducing onset of this disease. The protracted development (diagnosis is increas- ingly common between the ages of 50 and 70 years) and location of sporadic colorectal cancers in humans are problematic for conducting studies on the initiation and progression of this disease. Hence, a chemically in- duced colon cancer rat model is widely used to investi- gate the prevention and pathogenesis of this disease. The chemical carcinogen, dimethylhydrazine (DMH), produces pre-neoplastic aberrant crypt foci (ACF), and tumours in the colon of rodents [4]. Numerous stud- ies have focused on ACF lesions in rodents and humans 0006-291X/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2005.02.125 q Abbreviations: ACF, aberrant crypt foci; AC, aberrant foci; CA-II, carbonate anhydrase II; CBR, carbonyl reductase; DMH, dimethyl- hydrazine; EIA, enzyme immunoassay; MDA, malondialdehyde; TBARS, thiobarbituric acid reactive substances; TPM, tropomyosin. * Corresponding author. Fax: +44 1224 716629. E-mail address: jed@rri.sari.ac.uk (J.E. Drew). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 330 (2005) 81–87 BBRC