Adenosine AMD Guanosine 3′,5′ Cyclic Monophosphate Phosphodiesterase Activities in Rat Small and Large Bowel Following Single and Multiple Exposures to 1,2-Dimethylhydrazine

ABSTRACTThe hydrolytic activities of adenosine 3′,5′-cyclic mono-phosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP) phosphodiesterases (PDE) in rat large and small bowel tissue were determined after exposure to the colon carcinogen 1,2-dimethyl-hydrazine (DMH). Immediate increases in the cAMP-PDE activities were found in the tissues after a single exposure to the chemical which returned towards normal while chronic exposure resulted in no visible changes. The increased cAMP-PDE activities may be the factor responsible for the diminished intracellular cAMP concentrations found after exposure to the carcinogen. In contrast, the cGMP-PDE activities changed little in the colon and increased in the small bowel, suggesting that the determinant for the increases in the concentration cGMP was the activation of guany late cyclase enzymes following exposure to DMH. Ratios of cAMP to cGMP and cAMP-PDE to cGMP-PDE in the colon showed major changes after carcinogenic insult by the DMH, suggesting that su...