PHOTOREACTIVE (CAGED) CYCLIC-AMP ANALOGS INDUCE DNA-SYNTHESIS IN MAMMARY EPITHELIAL-CELLS

Dimethoxy-2-nitrobenzyl adenosine-3',5' cyclic monophosphate (DMNB) is a metabolically active, photolabile cyclic AMP analog that yields fre e cyclic AMP upon UV hydrolysis. The analog is useful in that it permi ts short term, transient elevations of intracellular cyclic AMP. Addit ion of DMNB (1-10 mu M) to mouse mammary epithelial cells, followed by UV irradiation of cells, caused a significant increase in DNA synthes is over that observed with controls, UV irradiation alone or DMNB alon e. In subsequent studies, DMNB exhibited a modest, but statistically s ignificant, interaction with epidermal growth factor in promoting DNA synthesis. Effects of DMNB were observed if DNA synthesis was measured as either H-3-thymidine incorporation into DNA or as percent S-phase cells. These results indicate that previously observed effects of agen ts such as cholera toxin and phosphodiesterase resistant cyclic AMP an alogs on mammary epithelial proliferation can be mimicked, at least in part, by a short term pulse of cyclic AMP.