Cell density dependence of cAMP and cGMP levels in four human cell lines derived from carcinomas of the uterine cervix.

Several studies have shown altered biokinetics of cyclic nucleotides in human cancer. In order to mimic the growing tumor bulk in carcinomas of the uterine cervix, four human cell lines (C4-I, C33A, ME-180, and SiHa) were expanded in serum-supplemented cell cultures. The extra- and intracellular levels of cAMP and cGMP were determined at increasing cell densities. In all of the cell lines, a cell density-dependent increase in the extracellular cGMP/cAMP ratio was observed. cAMP was distributed to the extracellular compartment against a concentration gradient at low cell densities but was retained in the intracellular compartment at high cell densities. In contrast, cGMP was distributed to the extracellular compartment against a concentration gradient for the whole range of cell densities. This study suggests that the cell density-dependent increase in the extracellular cGMP/cAMP ratio in cell lines derived from carcinomas of the uterine cervix is a result of changes occurring in both intracellular levels and cellular excretion of cyclic nucleotides.