Effect of hepatocarcinogens on the adenine purine nucleotide cycle during the initiation phase of carcinogenesis.
Activities of the adenine purine nucleotide cycle enzymes, i.e., adenylosuccinate (SAMP) synthetase, SAMP lyase, and adenosine 5'-monophosphate deaminse, were determined in hepatic tissue of rats fed and/or given injections of 3'-methyl-4-dimethylaminoazobenzene, 4'-methyl-4-dimethylaminoazobenzene, thioacetamide, ethionine, or 2-acetylaminofluorene. SAMP lyase activity showed an early increase in all regimens containing hepatocarcinogens. Adenosine 5'-monophosphate deaminse showed increases with 3'-methyl-4-dimethylaminoazobenzene and thioacetamide but not with ethionine or 2-acetylaminofluorene. SAMP synthetase either was nonresponsive or else showed inhibition to the carcinogens. Increase in SAMP lyase activity was noted as early as 48 to 72 hr following i.p. injections of these carcinogens. The response of SAMP lyase was not duplicated by analogs of carcinogens such as 4'-methyl-4-dimethylaminoazobenzene or methionine. These data imply interaction of active carcinogens with SAMP lyase and to some extent adenosine 5'-monophosphate deaminse or to some mechanism responsible for their synthesis and/or release. This interaction may be a significant component of the initiation phase of carcinogenesis.
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000659:AMP Deaminase / Q000378:metabolism*; D000264:Adenylosuccinate Lyase / Q000378:metabolism*; D000265:Adenylosuccinate Synthase / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D005001:Ethionine / Q000633:toxicity; D005260:Female; D008025:Ligases / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008190:Lyases / Q000378:metabolism*; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity; D009709:Nucleotide Deaminases / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D013853:Thioacetamide / Q000633:toxicity; D013997:Time Factors
D002273:Carcinogens; D013853:Thioacetamide; D008749:Methyldimethylaminoazobenzene; D015073:2-Acetylaminofluorene; D009709:Nucleotide Deaminases; D000659:AMP Deaminase; D008190:Lyases; D000264:Adenylosuccinate Lyase; D008025:Ligases; D000265:Adenylosuccinate Synthase; D005001:Ethionine