N1-METHYLNICOTINAMIDE LEVEL IN THE BLOOD AFTER NICOTINAMIDE LOADING AS FURTHER EVIDENCE FOR MALIGNANT-TUMOR BURDEN

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration Of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P < 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.