CHARACTERIZATION OF NICOTINAMIDE METHYLTRANSFERASE IN LIVERS OF MICE BEARING EHRLICH ASCITES TUMORS - PREFERENTIAL INCREASE OF ACTIVITY

There was a 2- to 7-fold increase in nicotinamide methyltransferase ac tivity in the livers of mice and rats bearing seven different kinds of tumors compared with the respective control normal livers, while acti vity in the tumors themselves was hardly detectable. The activity in t he liver started to increase markedly 3-7 days after i.p. transplantat ion of Ehrlich ascites tumors into the mice, maintaining a plateau up to death. Metabolic conversion of C-14-nicotinamide to C-14-N-1-methyl nicotinamide was 3-fold higher in the slices of the ascites tumor host liver than in the normal liver, but the conversion to other radioacti ve metabolites was not significantly different. Nicetinamide methyltra nsferase was finally purified 20,000-fold with a yield of 4% from the cytosolic fraction of the ascites tumor host liver by means of five pu rification steps. At every purification step, only one enzyme fraction was detected. The enzyme finally isolated exhibited a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, wit h a molecular weight of 26,000. As for the compounds investigated, inc luding the substrates for methyltransferases other than nicotinamide m ethyltransferase, only quinoline could be the substrate for enzyme act ivity. It is suggested that the increase in enzyme activity in the tum or host liver probably derived from the endogenous enzyme preexisting in the liver before tumor transplantation.