Changes in crypt cell DNA content during experimental colonic carcinogenesis

Abstract

Changes in colonic crypt cell DNA content have been monitored during experimental carcinogenesis. Colonic tumours were induced in Wistar rats using 12 consecutive subcutaneous injections of azoxymethane at a dose of 10 mg kg-1. Ten rats were killed at each of 10, 15, 20 and 25 weeks after the initial injection. On sacrifice the descending colon, plus any polyps or tumours with their adjacent mucosa, was removed, fixed and processed to paraffin wax. Sections were stained for DNA by the Feulgen reaction. Using an integrating microdensitometer the DNA content of the proliferative and functional cells was measured and expressed as a percentage of the stem cell DNA content. As carcinogenesis progressed there was an increase in the mean amount of DNA in the proliferative and functional cells in the distal colon although the tissue was histologically normal. The transitional mucosa adjacent to tumours showed the same increases as the 25 week distal colon. In the adenomas, there was a further increase in the DNA content of the functional cells. These results are probably a reflection of the increase in the number of dividing cells in the higher positions of the colonic crypts during carcinogenesis.