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T Christoffersen

Publications and source records attributed to T Christoffersen.

At least 91 records · Page 5Linked to original sources
PubMed1980

Effect of the antitumour agent 5-(3,3-dimethyl-1-triazeno imidazole-4-carboxamide (DTIC) on cyclic AMP levels in intact MH1C1 hepatoma cells.

Addition of the cytostatic agent 5-(3,3-dimethyl-1-triazeno)-imidazole-carboxamide (DTIC, dacarbazin) to MH1C1 hepatoma cells, alone or in combination with adrenaline, was shown to elevate intracellular cyclic AMP. The cyclic AMP level was increased from basal values of about 0.40 to about 0.75 pmol/mg protein 10 min. after DTIC addition. Accumulation of cyclic AMP in response to a supramaximal concentration of adrenaline is amplified in a dose-dependent way by 0.1-2 mM DTIC. The effect is apparently due to inhibition of cyclic AMP breakdown, since DTIC inhibits the low-Km form of the cyclic AMP phosphodiesterase without significantly affecting the adenylate cyclase activity of MH1C1 homogenates.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

On the role of cyclic AMP in the cytotoxic effect of fluoride.

The possible role of adenosine 3',5'-monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl-cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP-formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP.

Adenylyl Cyclases↗
PubMed1979

The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells.

The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Effect of prostaglandins and hormones on cyclic AMP formation in rat hepatomas and liver tissue.

The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices of normal liver, all the hepatomas responded strongly to PGE1 and PGE2. The hepatomas also had increase PGE1-sensitive adenylate-cyclase activity. PGF1alpha and PGF2alpha did not increase the cAMP level significantly either in the liver or in the hepatomas. During AAF carcinogenesis the response to PGE1 increased slightly during the carcinogen feeding, and was greatly elevated only in the fully developed hepatomas. This is in contrast to the increase in adrenalin response seen during carcinogenesis, which starts much earlier, and reaches a peak value within 8--10 weeks. It is concluded that various hepatomas have elevated responsiveness to PGE1 and PGE2 as well as to adrenalin, but the course of change in the tissues' ability to respond to these agents during carcinogenesis is very different.

Adenylyl Cyclases↗
PubMed1977

Scanning electron microscopic surface morphology of isolated hepatocytes from normal and premalignant rat liver.

Scanning electron microscopy was performed on hepatocytes isolated after collagenase perfusion of livers from rats fed 2-acetylaminofluorene (AAF) in the diet for 6--8 weeks and on hepatocytes from control rats. The premalignant AAF-cells showed a greater variation in cell size and shape. They also exhibited a reduced number of microvilli and more blebs and other protrusions on the surface than hepatocytes from control animals.

2-Acetylaminofluorene↗
PubMed1977

Role of cyclic nucleotides in human lymphocyte-mediated antibody-dependent cytotoxicity.

Experiments were carried out in order to throw light on the role of cyclic AMP and cyclic GMP in the modulation of the expression of antibody-dependent cytotoxicity mediated by human peripheral blood lymphocytes in vitro. Chicken erythrocytes were used as target cells. Support for an inhibitory role of cyclic AMP was derived from the marked suppression of cytotoxicity by dibutyryl cyclic AMP. Cyclic AMP itself had little effect. Isoproterenol, prostaglandin E1 and prostaglandin E2 increased cyclic AMP concentrations and strongly inhibited the cytotoxic effect of the lymphocytes. Histamine showed very slight elevation of the cyclic AMP level and suppression of the cytotoxicity. Theophylline did not increase the cyclic AMP concentration, but potentiated the effects of isoproterenol and prostaglandin E1 on the cyclic AMP levels, and significantly inhibited cytotoxicity. No clear effects were seen when cyclic GMP, dibutyryl GMP, acetylcholine or carbacholine were added to the cells. The results indicate that in this system cyclic AMP inhibits cytotoxicity, while no evidence for a role of cyclic GMP has been obtained.

Acetylcholine↗
PubMed1975

Altered hormone control of cyclic AMP formation in isolated parenchymal liver cells from rats treated with 2-acetylaminofluorene.

The hormone control of cyclic AMP-formation in isolated parenchymal liver cells from rats fed the carcinogen 2-acetylaminofluorene (0.025% for 4-8 weeks) was studied. The cells from the carcinogen-treated animals responded much more strongly to adrenergic agents than cells from control animals, while no significant difference was found for the glucagon effect. Of the adrenergic substances studied, the order of potency was isoprenalin larger than or equal to adrenalin larger than phhenylephrine; stimulation was blocked by propranolol, but not by phentolamine. The effects of supramaximal concentrations of isoprenalin and glucagon were not additive.

Animals↗