Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat.
It was previously reported that the properties of alcohol dehydrogenase of a rat hepatocellular carcinoma (Becker H-252), a tumor of intermediate growth rate, were different from those of the liver enzyme, suggesting different isozymes. To determine whether the degree of differentiation affected the isozyme of alcohol dehydrogenase, a fast-growing, poorly differentiated tumor and one that is well differentiated and of intermediate growth rate were studied. Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition. By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme. Thus, alcohol dehydrogenase is another example of an enzyme the isozyme composition of which changes with neoplastic de-differentiation. Further studies, including gel electrophoresis, substrate specificity patterns, and interaction with antibodies to alcohol dehydrogenase, are required to determine the factors responsible for the biochemical defect that occurs at the molecular level during carcinogenesis and whether the alcohol dehydrogenase isozymes in the Becker H-252 and Morris 7288ctc hepatomas are identical. A survey of several normal rat tissues revealed that only the stomach contains this unique isozyme of alcohol dehydrogenase.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002471:Cell Transformation, Neoplastic; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology; D051381:Rats; D013270:Stomach / Q000201:enzymology; D013737:Testis / Q000201:enzymology
D007527:Isoenzymes; D000429:Alcohol Oxidoreductases