Inhibition of adenovirus type 12 induced DNA synthesis in G1-arrested BHK21 cells by dibutyryl adenosine cyclic 3':5'-monophosphate.

Abstract

THE intracellular concentration of adenosine cyclic 3′ : 5′-monophosphate (cAMP) has been shown to increase in cells reaching confluency, that is, under conditions of contact inhibition and it has been proposed that contact inhibition may be mediated by the activation of adenyl cyclase1. Because loss of contact inhibition is one of the important characteristics of transformed cells, it is possible that variations in the level of cAMP play a crucial role in events associated with cell transformation. Growth of tumorigenic cell lines has been shown to be inhibited (80–90%) in the presence of cAMP1 and adenyl cyclase activity has been found to be much reduced in polyoma transformed cells2. BHK21 cells have been shown to be arrested in the G1-phase of the cell cycle after growth for 48 h in medium supplemented with serum at a low concentration (0.5%)3. BHK21 cells are non-permissive for infection with oncogenic adenovirus type 12 (Ad 12). Infection of a G1-arrested cell population with Ad12 results in induction of cellular DNA replication4, early virus mRNA is transcribed5, infected cells synthesize T antigen6, but no viral DNA synthesis7 late mRNA8, or viral capsid proteins8 can be detected after infection. Infection induces the cells to enter mitosis but the chromosomes break down and most of the cells die6. As a result, DNA synthesis is limited to a single burst4,6. Here we report the effects of dibutyryl-cAMP on induction of cellular DNA synthesis in G1-arrested BHK21 cells by infection with Adl2 or serum stimulation.