guanosine-monophosphate and Liver-Neoplasms

Topics: Adenosine Monophosphate; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Deoxyribonucleotides; Gene Expression Regulation; Gluconeogenesis; Guanosine Monophosphate; Humans; Inosine Monophosphate; Isoxazoles; Kidney Neoplasms; Liver Neoplasms; Liver Regeneration; Models, Biological; Neoplasms; Purines; Pyrimidines; Ribonucleotides

Dunning hepatoma has a low activity of deoxycytidylate deaminase, comparable to that of normal adult rat liver. This activity seems inconsistent with the rapid proliferation rate of the tumor. Factors which might affect the activity of deoxycytidylate deaminase in the Dunning hepatoma have been examined in it and compared to the Novikoff hepatoma which has high activity of this enzyme. The low activity in Dunning hepatoma does not appear to be the result of any inhibition or, possibly, proteolytic enzyme as judged by mixing experiments, nor does it appear to be due to in vivo differences in nucleotide concentrations especially deoxycytidine 5'-monophosphate, deoxycytidine 5'-triphosphate, or deoxyguanosine 5'-monophosphate which might either help stabilize the enzyme, allosterically increase its activity, or inhibit it. The Dunning hepatoma does not convert cytosine deoxyriboside to uridine deoxyriboside at a significant rate, and the formation of uridine deoxyriboside from deoxyuridine monophosphate is 1% or less during a 30-min incubation of high-speed supernatant fraction from the tumor in either the presence or absence of fluoride. It is concluded that the Dunning hepatoma probably has intrinsically low deoxycytidylate deaminase activity.

Topics: Animals; Carcinoma, Hepatocellular; DCMP Deaminase; Deoxycytidine Monophosphate; Deoxyuridine; Guanosine Monophosphate; Liver; Liver Neoplasms; Male; Neoplasms, Experimental; Nucleotide Deaminases; Rats

Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Animals; Carcinoma, Hepatocellular; Cell Membrane; Cyclic AMP; Fluorides; Glucagon; Guanosine Monophosphate; In Vitro Techniques; Liver; Liver Neoplasms; Magnesium; Neoplasms, Experimental; Rats; Temperature