Study of Cell Kinetics in the Normal Colorectal Mucosa of Subjects at Risk of Developing Colorectal Carcinoma

Abstract

This report examines the ³H-thymidine-labeling index (LI), the flow cytometric S-phase cell fraction, and DNA ploidy in the normal colorectal mucosa of three groups of subjects: normal subjects (group A), patients with adenomas (group B) and patients with cancer (group C). The total LI and the LI for crypt compartment were investigated. The former LI was similar in the three groups while that for crypt compartment was significantly higher in the patients with adenomas (compartment 3), and in those with cancer (compartments 3 and 4). All of the mucosas were diploid and no significant relationship was found between the LI and the flow cytometric S-phase values, considered for each group. These data suggest that an upwards expansion of the proliferative compartment seems to be an indicator of cancer risk. In contrast, the variations of the ploidy and S-phase fraction do not appear to be important risk factors in the three groups of subjects studied.

Effect of tumor removal on mucosal protein synthesis in patients with colorectal cancer

“…The tracer-to-tracee values of [1][2][3][4][5][6][7][8][9][10][11][12][13] C]leucine in tissue protein and in the free, intracellular amino acid pool at the two sampling points are presented in Table 1.…”

“…Thus some authors reported an increased percentage of cells in the S-or M-phase in seemingly normal mucosa of patients with sporadic colorectal cancer when 5-bromodeoxyuridine or [ 3 H]thymidine incorporation was determined (2,16,18,23,26) or when mitoses were counted (20). On the other hand, using the same or similar (PCNA staining) histochemical methods, other investigators were unable to demonstrate such significant differences between mucosa from patients with colorectal cancer and that from healthy subjects (4,15,27). Therefore, it is possible that, besides a growing number of proliferating cells, also an accelerated cell cycle contributed to the increased protein synthetic rate and thus to the hyperproliferative state of grossly normal mucosa in cancerbearing patients.…”

“…At stage II, the maximum of the proliferative compartment shifts to the upper portion of the crypt, and, at stage III, the total number of replicating cells in the crypt rises, leading to mucosal hyperproliferation and subsequently, because of the influence of cofactors, to neoplastic transformations (adenoma). However, in patients with sporadic colorectal cancer, findings are controversial, and the scientific literature is divided into reports supporting (2,18,20,23,26) or contesting (1,4,15,21,22,27) the importance of the stage III defect for adenoma and carcinoma formation.…”