Telomerase activation and cell proliferation during 7,12-dimethylbenz[a]anthracene-induced hamster cheek pouch carcinogenesis.

Abstract

Telomerase is a ribonucleoprotein complex intimately involved in cell immortalization and carcinogenesis. This enzyme is activated and stabilizes telomere length in almost all types of cancer. Telomerase may be necessary for continuous cell proliferation. In this study, we analyzed telomerase activity in hamster experimental oral lesions (starting from epithelial hyperplasia through dysplasia, carcinoma in situ, and invasive carcinoma) evoked by 7,12-dimethylbenz[a]anthracene, and in normal mucosa. We also analyzed proliferative activity in these lesions by using immunohistochemical analysis and flow cytometry. Histologically normal epithelium expressed weak telomerase activity. The telomerase activity count increased rapidly in the early stage of carcinogenesis and gradually in the late stage. Cell-proliferative activity closely correlated with progression of disease. These findings indicate that telomerase activation is an early event and that increases in telomerase activity upregulate cell proliferation in chemically induced hamster oral carcinogenesis.