Effects of carcinogenesis on colonic thymidine kinase activity in familial adenomatous polyposis

Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of non-tumorous colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of non-tumorous colon; its increase seems attributable mainly to increased activity of cytosolic TK isozyme activity. By using DEAE-cellulose column chromatography, the colorectal TK isozymes were separated into two types, i.e. two isozymes, referred to as the fetal (predominantly cytosolic) and adult (predominantly mito-chondrial) types. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over non-tumorous region of colon. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity, which was elevated in some cases (8/15) and remained low in others. Thus FAP polyps seem to be a heterogeneous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.