Significance of the labeling index and labeling distribution as kinetic parameters in colorectal mucosa of cancer patients and DMH treated animals

To shed light on the more elevated labeling index (LI) found in the normal appearing mucosa of a group of colon cancer patients previously reported by Maskens and Deschner, the same data together with that from patients with an isolated adenoma, DMH treated CF1 mice and BD IX rats were analyzed on the basis of individual crypt values. One of 13 control patients had crypt values over 15% in contrast to 17 of the 26 cancer and polyp patients (P < 0.05). Crypts in control patients regardless of LI values showed some extension of the normal proliferative compartment from the lower two‐thirds to the upper third of glands (Stage I abnormality). In cancer patients, crypts with a low of 6–8% or a high of >15% revealed the Stage I defect in addition to an upward shift in the major zone of DNA synthesis from the lower to the middle and upper thirds of glands (Stage II abnormality), although both abnormalities were more emphatically expressed in glands with a high LI. Individual crypts in DMH treated mice had LI far higher than controls whereas no real differences in crypt LI were found between DMH treated rats and controls. Similar to colon cancer patients, both categories of crypts in DMH treated mice had the Stage I and II proliferative defects. Crypts in DMH treated rats, however, showed a downward shift of the major zone of DNA synthesis from the middle and upper third of glands. That DMH induces primarily microinvasive carcinomas in rats while in mice predominantly adenomas form, a proportion of which becomes malignant, would suggest a relationship between the direction of the shift of the major zone of proliferation and the type lesion induced. In man and mouse, hyperactive crypts would have a selective advantage over other glands allowing earlier expression of neoplastic transformation within them. Furthermore, their recognition as a marker along with the Stage II defect may be useful in tissues at high risk for colorectal tumorigenesis.