Increased cyclic AMP levels in malignant hepatic nodules of ethionine treated rats

Chayoth, Reuben; Epstein, Sheldon M.; Field, James B.

doi:10.1016/0006-291x(72)90534-7

Cited by 32 publications

(9 citation statements)

References 15 publications

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“…Thus, in earlier studies we found higher adenylate cyclase and cAMP levels in adenomas and carcinomas of the human thyroid than in the surrounding uninvolved gland (22,23). Similarly, while some rat hepatomas have reduced cAMP or increased cGMP (19,21), in others cAMP has been the same or higher than that of the surrounding liver (18)(19)(20). Moreover, under certain experiment conditions, cAMP has been implicated as a positive rather than negative signal for hepatocyte growth (41,42), and in the rapidly proliferating crypt cells of intestinal mucosa, adenylate cyclase activity has been reported to be higher than that of the more slowly growing superficial cells (43 (46,47), and an altered response pattern to hormonal stimuli (20,35,48,49) have now all been observed in neoplastic tissues.…”

Section: Methodsmentioning

confidence: 70%

“…According to this concept, derived primarily from studies of cultured cells, a reduction in cAMP, an increase in cGMP, or both might be predicted in tissue that has undergone malignant transformation. Determination of cyclic nucleotide levels in experimentally induced tumors, particularly rodent hepatomas, has not revealed a consistent pattern of alteration in cyclic nucleotide content relative to that of the surrounding normal tissue (18)(19)(20)(21). However, only limited data are available on cyclic nucleotide levels or the regulation of cyclic nucleotide metabolism in naturally occurring neoplasms of man (22,23).…”

Section: Introductionmentioning

confidence: 99%

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The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

DeRubertis¹,

Chayoth²,

Field³

1976

J. Clin. Invest.

114

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Section: Methodsmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

DeRubertis¹,

Chayoth²,

Field³

1976

J. Clin. Invest.

114

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“…P-adrenoceptors increased in number, and their responsiveness to isoproterenol also increased under a proliferative state such as hepatocarcinogenesis (Refsnes et al, 1986). Increased activity of the adenylate cyclase and elevated levels of cAMP in the liver were found during the induction of hepatocarcinogenesis with various agents such as 2-AAF, aminoazobenzenes and ethionine (Chayoth et al, 1972;Christoffersen et al, 1972Christoffersen et al, , 1974Boyd et al, 1974;Christoffersen, 1975;Christoffersen and Berg, 1975;Boyd and Martin, 1976; DeRubertis and …”

Section: Discussionmentioning

confidence: 95%

Enhancement by isoproterenol of hepatocarcinogenesis induced by n‐nitrosomorpholine in sprague‐dawley rats

Uehara

Nakaizumi

Baba

et al. 1993

Intl Journal of Cancer

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The effect of isoproterenol on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and s.c. injections of isoproterenol or vehicle every other day for 13 weeks. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 13. Prolonged administration of isoproterenol resulted in a significant increase in the number of GGT-positive, but not GST-P-positive, lesions. The incidence, number and size of hepatocellular carcinomas were also significantly greater in rats treated with isoproterenol than in controls. Administration of isoproterenol significantly increased the intracellular cAMP and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that isoproterenol enhances hepatocarcinogenesis and that this may be related to its enhancing effect, mediated by cAMP, on cell proliferation in neoplastic lesions and surrounding hepatocytes.

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“…The adenylyl cyclase system has also been studied with various other transplantable tumors and carcinogen-induced primary hepatomas such as: 484A (rapidly growing) and 147042 (slow growing) (59); Ehrlich ascites (11); Zajdela ascites (103); Yoshida ascites (201); ascites hepatomas 7974, 37lA, 130 (139); 2-acetylaminofluorene-induced (37-40); 3-methyl-4-dimethylaminoazobenzene-induced (17,18); and ethionine-induced (28,52). Most of these tumors also demonstrated a decrease in glucagon responsiveness and an increase in epinephrine responsiveness.…”

Section: Metabolism Of Cyclic Nucleotides Synthesis Adenylyl Cyclase mentioning

confidence: 99%

Regulation of Cyclic AMP and Cyclic GMP in Morris Hepatomas and Liver

Hickie

1978

Morris Hepatomas

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SUMMARYStudies on the regulation of tissue levels and action of adenosine 3':5'-monophosphate (cyclic AMP) and cyclic guanosine 3':5'-monophosphate (cyclic GMP) in Morris hepatomas and liver have been reviewed. Though the data is incomplete in some areas, the following generalizations can be made. A prominent difference between Morris hepatomas and normal liver, in relation to cyclic AMP formation, is the decreased responsiveness of tumor adenylyl cyclase to glucagon. This characteristic is most marked in rapidly growing hepatomas and appears to be associated with diminished plasma membrane binding of glucagon; regenerating liver and fetal liver resemble hepatomas in their responsiveness to glucagon. The responsiveness of adenylyl cyclase to epinephrine is, in contrast, generally enhanced in hepatomas as well as in regenerating and fetal liver. Marked increases in particulate guanylyl cyclase activities, relative to corresponding soluble activities, are seen consistently in Morris hepatomas and in regenerating and fetal liver; in the latter tissues, increases in plasma membrane guanylyl cyclase activities can be correlated with increased proliferative activity. Although the total cyclic AMP phosphodiesterase activities are significantly reduced in all Morris hepatomas examined, the activities of the high affinity (low Km) cyclic AMP phosphodiesterase in plasma membranes from some Morris hepatomas are higher than those of normal liver. The degradation of cyclic GMP by Morris hepatomas is also impaired, most notably in the particulate fractions. In regenerating and fetal liver the activities of cyclic AMP and cyclic GMP phosphodiesterases are, in contrast, not changed appreciably. The ratios of cyclic GMP levels, relative to cyclic AMP, tend to be higher in Morris hepatomas than in normal liver. Though these ratios are highest in rapidly growing hepatomas, the correlation between cyclic nucleotide levels and tumor growth rate is not strong. The correlation between cyclic GMP/cyclic AMP ratios and hepatocyte proliferation is controversial at this time; the most recent studies on regenerating liver suggest that these ratios are increased prior to the proliferative phase. Only a few studies have been carried out on cyclic nucleotide binding proteins and kinases. These studies indicate that: cytosols from rapidly growing hepatomas have a reduced ability to bind cyclic AMP with increased (?) binding of cyclic GMP; there is a positive correlation between cyclic AMP binding and tumor sensitivity to growth inhibition by dibutyryl cyclic AMP; cytosol fractions from rapidly growing hepatomas generally have reduced cyclic AMP dependent protein kinase activities and increased endogenous (cyclic AMP independent) kinase activities.

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Increased cyclic AMP levels in malignant hepatic nodules of ethionine treated rats

Cited by 32 publications

References 15 publications

The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

Enhancement by isoproterenol of hepatocarcinogenesis induced by n‐nitrosomorpholine in sprague‐dawley rats

Regulation of Cyclic AMP and Cyclic GMP in Morris Hepatomas and Liver

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