Effect of pharmacological agents on human keratinocyte mitosis in vitro. I. Inhibition by adenine nucleotides.

Abstract

In the last few years many studies have suggested that cyclic adenosine 3': 5' monophosphate (cyclic AMP) may be specifically involved in regulation of proliferation and differentiation of many types of mammalian cells in vitro (1-4). In organ cultures of mouse skin, the reduction of epidermal mitosis by epinephrine is associated with an increase in adenyl cyclase activity (5, 6). This finding supports results in other in vitro systems showing that increased cyclic AMP levels are inhibitory to cellular proliferation (1, 4). Recently, Voorhees et al. (7), showed that dibutyryl cyclic AMP, but not 5'-AMP, inhibited epidermal cell division in mouse skin in organ culture. Using HeLa and L cells, Ryan and Heidrick (1) reported inhibition of cell growth by cyclic AMP but not by 5'-AMP or adenosine. Others who have investigated the role of cyclic AMP in cellular function either found no effect of 5'-AMP, ADP and ATP, or found that these nucleotides are toxic to cells (1, 2, 8). Thus, specificity of cyclic AMP ha...