Abstract
A novel variant of S49 mouse lymphoma cells is described which is resistant to growth arrest and cytolysis by dibutyryl cyclic AMP but, in contrast to previously described variants, has normal cyclic AMPβdependent protein kinase. The variant is also resistant to N^6^βmonobutyryl cAMP but is sensitive to killing by 8βbromo cAMP and cholera toxin. Extracts of the variant appear to contain wild type levels of both O^2^β²βbutyrylesterase and cyclic AMP phosphodiesterase activities. Accumulation of exogenous [^3^H]dibutyryl cyclic AMP is reduced in the variant suggesting a defect in either uptake or secretion of the analog or its metabolic products. Accumulation of cyclic AMP in variant cells after stimulation of adenylate cyclase with either isoproterenol or cholera toxin is also reduced compared with wild type cells, although cyclase activity of membranes prepared from the variant cells is normal. Extracellular accumulation of cyclic AMP after stimulation of variant cells with isoproterenol is greater than that found with wild type cells. It is concluded that the variant has an alteration in its cyclic AMP secretion mechanism resulting in more efficient extrusion of cyclic AMP than in wild type cells.