cyclic-gmp and Precancerous-Conditions

Topics: Aging; Base Sequence; Caffeine; Carcinogens; Cell Differentiation; Cell Division; Chromatin; Chromosome Aberrations; Cyclic AMP; Cyclic GMP; DNA Nucleotidyltransferases; DNA Repair; DNA Replication; Endonucleases; Environment; Genetic Diseases, Inborn; Humans; Models, Biological; Mutagens; Mutation; Neoplasms; Phenotype; Phorbol Esters; Precancerous Conditions; Recombination, Genetic; Ultraviolet Rays

The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the

Topics: Adenomatous Polyposis Coli; Animals; Apoptosis; Cell Proliferation; Cell Transformation, Neoplastic; Cyclic GMP; Female; Guanylyl Cyclase C Agonists; Intestinal Neoplasms; Male; Mice; Mice, Inbred C57BL; Peptides; Precancerous Conditions; Sildenafil Citrate

l-Arginine is metabolized either to polyamines through arginase and ornithine decarboxylase (ODC) activities or to citrulline and nitric oxide (NO, nitrogen monoxide) through the NO synthase (NOS) pathway. Polyamine levels and ODC activity are high in tumor cells. The aim of this study was to test whether N(G)-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NOS, modulates colon carcinogenesis. Adult male Wistar rats were treated with azoxymethane (AOM, 15 mg/kg ip), a chemical carcinogen, once a week for 2 weeks. One week after the second injection the rats were randomly divided into two groups. One group (n = 8) received l-NAME (10 mg/kg body wt/day) in drinking water. The control group (n = 8) received tap water. After 5 weeks, the rats receiving l-NAME showed enhanced mean basal arterial blood pressure, decreased heart rate, and a significant decrease of the cGMP content in the colonic mucosa. In both groups, AOM induced the formation of colonic aberrant crypt foci (ACF). In l-NAME-treated rats, the number of ACF was higher than in controls by 47%. ODC activity was enhanced by 11-fold. S-Adenosyl-methionine-decarboxylase activity and putrescine concentration were significantly increased in the colonic mucosa of l-NAME-treated rats. The data suggest that l-NAME promotes carcinogen-induced preneoplastic changes in the colon by inhibiting NOS activity and by stimulating polyamine biosynthesis.

Topics: Adenosylmethionine Decarboxylase; Animals; Azoxymethane; Biogenic Polyamines; Blood Pressure; Body Weight; Carcinogens; Colon; Cyclic GMP; Enzyme Inhibitors; Heart Rate; Intestinal Mucosa; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Ornithine Decarboxylase; Precancerous Conditions; Putrescine; Rats; Rats, Wistar; Spermidine; Spermine

Urinary excretion of cyclic GMP (cGMP) and the plasma level of cyclic AMP (cAMP) were determined in patients with liver diseases. The urinary excretion of cGMP, expressed on the basis of creatinine excreted per day, was at significantly higher levels not only in primary hepatoma but also in liver cirrhosis, while the plasma level of cAMP was higher only in liver cirrhosis. Thus, the ratio of urinary cGMP excretion to plasma cAMP level in primary hepatoma was significantly higher than that in liver cirrhosis. In cirrhotic patients studied by catheterization, the level of cGMP in the hepatic vein was significantly lower than that in the superior mesenteric or portal vein, indicating the uptake of cGMP by the liver. Since cGMP excretion correlated with KICG both in liver cirrhosis and primary hepatoma, the increased cGMP excretion appeared to be explained by a reduced uptake of cGMP by the liver.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Cyclic AMP; Cyclic GMP; Female; Hepatitis; Humans; Liver Neoplasms; Male; Middle Aged; Precancerous Conditions

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.

Topics: Adenocarcinoma; Animals; Colonic Neoplasms; Cyclic AMP; Cyclic GMP; Dimethylhydrazines; Injections, Subcutaneous; Intestinal Neoplasms; Kinetics; Male; Precancerous Conditions; Rats