In utero effects of 1,2-dimethyl hydrazine on adenosine and guanosine 3′,5′-cyclic monophosphate content in rat fetal intestine

Abstract Sperm positive 12–14-day pregnant Holtzman rats were exposed to a single subcutaneous injection (20 mg/kg body wt) of 1,2-dimethylhydrazine (DMH). Two days post-exposure, the fetal intestinal tissues were examined for their content and metabolic activities for cyclic 3′,5′-adenosine monophosphate (cAMP) and cyclic 3′,5′-guanosine monophosphate (cGMP). The in utero exposure to the carcinogen resulted in lowering the intracellular content of cAMP and increasing cGMP. The decreased levels of cAMP may be accounted for the finding of a corresponding increase in its breakdown by its phosphodiesterases; however, associated with the increase in cGMP was correspondingly an increase in its phosphodiesterases, suggesting the activities for synthesis of this cyclic nucleotide may be the major factor for its elevated concentration. These observations indicate that DMH may cross the placental barrier and can effect the intracellular cyclic nucleotide concentrations in the fetal tissues as well as acting as a colorectal carcinogen in the adult rat. The changes in the cyclic nucleotide levels were toward the direction expected for an increased cell proliferation; consequently, further investigations are suggested to determine whether a hyperproliferative state is induced by the DMH in the already rapidly dividing fetal intestinal tissue.