Altered distribution and excretion of N-1-methylnicotinamide in rats with Walker 256 carcinosarcoma.

ABSTRACT

Levels of nicotinamide and N-1-methylnicotinamide in serum, liver, and kidney as well as renal clearances and 24-hr urine levels of N-1-methylnicotinamide were compared in normal rats and rats bearing Walker 256 tumors. There was no significant difference between normal and tumor-bearing rats with regard to nicotinamide levels. With regard to N-1-methylnicotinamide, tumor-bearing rats had significantly lower serum and liver levels and significantly higher 24-hr urine levels and renal clearances. Walker 256 tumor tissue and liver and kidney from a normal and a tumor-bearing rat were separately examined for S-adenosylmethioninenicotinamide methyltransferase activity. The specific activity in tumor tissue extract was greater than that in each liver extract, which, in turn, was much greater than the specific activity in each tissue (liver and kidney) from the tumor-bearing rat was equal to the specific activity in the corresponding tissue of the normal rat. S-adenosylmethioninenicotinamide methyltransferase was obtained with 18-fold purification from a tissue extract of Walker 256 tumor. The enzyme activity required activation by thiols, and maximal activity was observed at pH 8.6. The Km's for the substrates, S-adenosylmethionine and nicotinamide, were 7.0 x 10--3 mM and 0.50 mM respectively. The Ki's for the products, S-adenosylhomocysteine and N-1-methylnicotinamide, were respectively, 25 x 10--3 mM and greater than 5 mM.