N1-METHYLNICOTINAMIDE LEVEL IN THE BLOOD AFTER NICOTINAMIDE LOADING AS FURTHER EVIDENCE FOR MALIGNANT-TUMOR BURDEN
N1-METHYLNICOTINAMIDE LEVEL IN THE BLOOD AFTER NICOTINAMIDE LOADING AS FURTHER EVIDENCE FOR MALIGNANT-TUMOR BURDEN
复制标题
DOI：
10.1111/j.1349-7006.1991.tb01793.x
复制
发表时间：
1991-11-01
期刊：
影响因子：
--
通讯作者：
FUJIMURA, S
中科院分区：
文献类型：
--
作者：
NAKAGAWA, K;MIYAZAKI, M;FUJIMURA, S
Ehrlich腹水肿瘤（腹水型）腹腔移植后小鼠肝脏中烟酰胺甲基转移酶（Nmd - ch3转移酶）活性升高，而d -半乳糖胺诱导急性炎症小鼠肝脏中Nmd - ch3转移酶活性不升高，四氯化碳诱导小鼠肝脏中Nmd - ch3转移酶活性降低并出现坏死。在原代培养大鼠肝细胞中添加地塞米松、表皮生长因子、转化生长因子- β、肿瘤坏死因子- α和n1 -甲基烟酰胺（1-CH3Nmd）后，研究Nmd ch3转移酶活性的变化与DNA合成无相关性，提示肿瘤宿主肝脏中该酶活性的升高与肝细胞增殖无直接关系。因此，为了利用该酶活性的增加作为肿瘤负荷标志物，我们建立了一种通过测定Nmd ch3转移酶产生的Nmd代谢物1-CH3Nmd的血液水平来估计其水平的方法。在埃利希腹水肿瘤发生的早期至晚期，腹腔注射Nmd （500 mg/kg体重）4 h后，小鼠血液中1-CH3Nmd水平与肝脏中该酶活性密切相关（r = 0.835, P < 0.00001）。此外，在携带其他各种肿瘤的动物组中也发现了类似的相关性，如s.c.植入的埃利希腹水瘤（实体形式）和i.p.植入的肉瘤S-180、肝癌MH-134、吉达腹水肉瘤和白血病L-1210，但没有实体肿瘤，如Lewis肺癌和黑色素瘤B-16，尽管几乎所有携带这些肿瘤的动物都显示出比正常对照动物更高的酶活性。
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.