Growth characteristics of autochthonous experimental colonic tumors as assessed by serial colonoscopic measurement in rats

Abstract

We report the growth characteristics of autochthonous experimental colonic tumors as assessed by serial measurements at colonoscopy. Male Fischer 344 rats were given 10 weekly subcutaneous injections of the bowel carcinogen azoxymethane, 10 mg/kg (weeks 1–10). Beginning in week 15, colonoscopy to the splenic flexure was performed weekly with a pediatric fiberoptic bronchoscope. Width of identified tumors was measured in photographs that included a scale passed through the biopsy channel, and tumor volume was calculated using computerized image analysis. Sensitivity, specificity, predictive values, and efficiency of colonoscopy for identification of tumors were 85%–100%. Cumulative tumor incidence in the descending colon increased in a relatively linear fashion from 3% at week 15 to 68% at week 30. Tumor width by colonoscopy correlated well with width at necropsy (r = 0.951). Growth curves of individual tumors were highly variable; however, tumor width showed stable mean weekly growth rates. By contrast, mean calculated tumor volume rose exponentially, with deviation from the fitted curve in the sixth week. All tumors >3 mm in width or >10 mm3 in volume showed invasion. Final tumor width and volume, and growth of tumor volume during the initial week but not the later weeks of observation, correlated with depth of invasion. Our findings suggest that (a) colonoscopic measurement was useful to study the growth characteristics of autochthonous experimental colonic tumors; (b) azoxymethane administration produced persistently altered colonic epithelium that had variable latent periods until development of visible tumors in individual rats; (c) the growth curves of individual colonic tumors were exponential, although variable, during the initial weeks; (d) invasion was found in small tumors and depth of invasion correlated with growth rate during the initial week but riot the later weeks. This aggressive behavior of the tumors early in their course contrasts with colorectal adenomas in humans and argues against the routine occurrence of an adenoma-carcinoma sequence in the model we used.