Intracellular adenosine and guanosine 3',5'-cyclic monophosphate concentrations in rat small and large bowel following single and multiple exposures to 1,2-dimethylhydrazine.
The adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels were determined in the small and large intestinal tissue of rats that had been exposed to single and chronic administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). A single subcutaneous injection of DMH resulted in a decrease in the intracellular concentration of cAMP and increase in cGMP beyond the levels which had been measured in the unexposed intestinal tissue and DMH induced intestinal adenocarcinomas. Recovery to normal concentrations of the cyclic nucleotides occurred within 30 days. Multiple exposures resulted in maintaining reduced levels of cAMP while cGMP was also found to be lowered upon the chronic administration. A possible explanation for these observations is the expansion of the crypt cell population consisting of replicating intestinal cells that occurs upon exposure to the carcinogen. These findings suggest that cyclic nucleotide alterations may represent a characteristic of the precancerous state of intestinal tissue and indicates further studies are warranted to determine whether these changes may serve as a useful marker in a screening program for colon cancer.
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000378:metabolism; D007279:Injections, Subcutaneous; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism; D051381:Rats
D004127:Dimethylhydrazines; D000242:Cyclic AMP; D006152:Cyclic GMP