COMPARISON OF THE AGE- AND TUMOR-ASSOCIATED CHANGES IN THE C-MYC GENEMETHYLATION IN MOUSE-LIVER

Study of DNA methylation of the c-myc gene in liver tumors of BCF1 mic e treated with various agents revealed frequent alteration from that i n normal liver. The alteration, however, was complex and showed either an increase or a decrease of methylation to various degrees. On the o ther hand, the tumors obtained from middle-aged C3H/He mice, which dev elop liver tumors spontaneously at a high incidence rate starting in m iddle age, showed predominantly increases of methylation in the c-myc gene, while the large tumors found in older mice revealed decreases. T he normal part of the liver showed a slight gradual age-dependent incr ease. These suggest that hypermethylation of the c-myc gene is common to aging and early tumor development in liver. Thus the alteration of DNA methylation seems to be a good clue to investigate why the tumor i ncidence rate increases rapidly as individuals grow older.