Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woodchuck hepatitis virus.
Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woodchuck hepatitis virus.
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发表时间：
1992-08
期刊：
影响因子：
11.2
通讯作者：
R. Liu;J. Jacob;B. Tennant;J. Hotchkiss
中科院分区：
文献类型：
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作者：
R. Liu;J. Jacob;B. Tennant;J. Hotchkiss
从土拨鼠 (Marmota monax) 中分离出的肝细胞经脂多糖 (LPS) 刺激后，可在体外从 L-精氨酸产生亚硝酸盐。从作为土拨鼠肝炎病毒慢性携带者的土拨鼠中分离出的肝细胞形成的亚硝酸盐是来自未感染动物的肝细胞的两倍。肝细胞的亚硝酸盐合成与组织培养基中的 L-精氨酸和 LPS 浓度直接相关，并在 0.5 mM L-精氨酸和 1.0 微克/ml LPS 时达到稳定水平。 LPS 刺激的肝细胞在 L-精氨酸存在、生理 pH 值 7.4 的情况下亚硝化吗啉形成 N-亚硝基吗啉。当亚硝酸盐和吗啉直接添加到培养基中时，在类似条件下，用LPS刺激肝细胞时，与未刺激的肝细胞相比，N-亚硝基吗啉产量增加10倍。 NG-monomethyl-L-arginine 是一氧化氮合酶的选择性抑制剂，可抑制亚硝酸盐和 N-亚硝基吗啉的形成。这些结果表明，亚硝化剂是通过 L-精氨酸-一氧化氮途径在肝细胞中形成的。这表明致癌N-亚硝基化合物的内源性形成可能影响慢性土拨鼠肝炎病毒感染的土拨鼠的肝癌发生过程。
Hepatocytes isolated from woodchucks (Marmota monax) were shown to produce nitrite in vitro from L-arginine after stimulation with lipopolysaccharide (LPS). Hepatocytes isolated from woodchucks that were chronic carriers of woodchuck hepatitis virus formed twice as much nitrite as hepatocytes from noninfected animals. Nitrite synthesis by hepatocytes was directly related to L-arginine and LPS concentrations in the tissue culture medium and reached a plateau at 0.5 mM L-arginine and 1.0 micrograms/ml LPS. LPS-stimulated hepatocytes nitrosated morpholine to form N-nitrosomorpholine in the presence of L-arginine at a physiological pH of 7.4. There was a 10-fold increase in N-nitrosomorpholine production when hepatocytes were stimulated with LPS compared to unstimulated hepatocytes under similar conditions when both nitrite and morpholine were directly added to the medium. NG-monomethyl-L-arginine, a selective inhibitor of nitric oxide synthase, inhibited formation of both nitrite and N-nitrosomorpholine. These results demonstrate that nitrosating agents are formed in hepatocytes via the L-arginine-nitric oxide pathway. This suggests that endogenous formation of carcinogenic N-nitroso compounds could influence the process of hepatocarcinogenesis in woodchucks with chronic woodchuck hepatitis virus infection.