Positive correlation between the extent of cell proliferation and the regulation of base excision repair

The regulation of base excision repair during cell proliferation was examined as a function of the rate of cell growth. Normal human skin fibroblasts (mean generation time, 27.64 hr) and hamster fibroblasts (mean generation time, 13.79 hr) were utilized to examine this relationship. The regulation of base excision repair in each cell type was examined by quantitating (a) the activity of the base excision repair enzyme, uracil DNA glycosylase, during asynchronous cell proliferation; and (b) glycosylase activity during cell proliferation after exposure to dimethyl sulfate. In both cell types, uracil DNA glycosylase was increased as a function of cell proliferation. The extent of enhancement was greater in the baby hamster kidney cells than in the normal human skin cells (9.5-fold versus 4-fold, respectively). In baby hamster kidney cells, cell proliferation as well as the enhancement of uracil DNA glycosylase was unaffected by exposure to 20 microM dimethyl sulfate. In contrast, the exposure of normal human skin cells to 20 microM dimethyl sulfate reduced the extent of cell growth and, consequently, the proliferative-dependent stimulation of uracil DNA glycosylase. These results suggest that the regulation of base excision repair is directly proportional to the proliferative rate characteristic of a given cell population.