Inhibition by acetaminophen of neoplastic initiation elicited in rat liver by the DNA-reactive hepatocarcinogen N-acetyl-2-aminofluorene.
Inhibition by acetaminophen of neoplastic initiation elicited in rat liver by the DNA-reactive hepatocarcinogen N-acetyl-2-aminofluorene.
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对乙酰氨基酚对 DNA 反应性肝癌 N-乙酰基-2-氨基芴在大鼠肝脏中引起的肿瘤起始的抑制作用。
DOI：
10.1097/01.cej.0000243854.12728.b8
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Perrone,CarmenE
中科院分区：
文献类型：
--
作者：
Williams,GaryM;Iatropoulos,MichaelJ;Jeffrey,AlanM;Duan,Jian-Dong;Perrone,CarmenE
扑热息痛是一种单环酚类化合物和镇痛剂，在饲料中以8900 ppm的浓度饲喂时，报告了抑制芳香胺类化合物N-羟基-N-乙酰基-2-氨基荧致大鼠肝癌的作用。为了阐明这种抗癌作用的机制(S)，本研究检测了较低剂量的对乙酰氨基酚是否有能力抑制肝癌前体N-乙酰-2-氨基荧烯对大鼠肝脏的启动作用。将雄性F344大鼠随机分为6组，每组10只，每组10只，每组10只，每周3天，以2.6 mg/kg剂量灌胃给药8周，每周3天。在饲喂N-乙酰-2-氨基荧前1周开始，单独给予2400或4800ppm的对乙酰氨基酚9周(第2组和第3组)，或添加N-乙酰-2-氨基荧组(第5组和第6组)。在这两种饮食浓度下，对乙酰氨基酚的血药浓度分别为1和4μg/ml。N-乙酰-2-氨基荧致肝细胞癌前病变作为肝细胞变性灶，表达谷胱甘肽S转移酶-P，反映起始。两种浓度的对乙酰氨基酚均可减少诱发病灶。对乙酰氨基酚本身不产生DNA加合物，也不改变N-乙酰-2-氨基荧烯-DNA加合物的高度形成，通过核苷酸后标记测量，约为108个核苷酸中的200个。对乙酰氨基酚不影响背景肝细胞的增殖，但显著降低N-乙酰-2-氨基荧促增殖的增殖细胞核抗原免疫染色检测。因此，扑热息痛有效地保护肝细胞免受N-乙酰-2-氨基荧烯的启动效应，可能是通过减缓诱导细胞周转速度而产生的细胞保护作用。
Acetaminophen, a monocyclic phenolic compound and analgesic, when fed at 8900 ppm in the diet, was reported to inhibit the hepatocarcinogenicity in rats of the aromatic amine proximate carcinogen N-hydroxy-N-acetyl-2-aminofluorene. To elucidate the mechanism (s) of this anticarcinogenicity, the present study examined whether acetaminophen at lower doses has the ability to inhibit the initiating effects in the rat liver of the precursor hepatocarcinogen N-acetyl-2-aminofluorene. Male F344 rats were allocated to six groups, which were maintained under reverse light cycle conditions to assure acetaminophen ingestion at the time of N-acetyl-2-aminofluorene administration during the dark phase, which was imposed from 07.00 to 19.00 h. Group 1 served as vehicle control (0.5% carboxymethylcellulose) for N-acetyl-2-aminofluorene, which was administered intragastrically 3 days per week at 2.6 mg/kg for 8 weeks (group 4) to achieve initiation. Acetaminophen was given in the diet either alone at 2400 or 4800 ppm for 9 weeks (groups 2 and 3), or with N-acetyl-2-aminofluorene (groups 5 and 6), starting 1 week before N-acetyl-2-aminofluorene administration. Acetaminophen blood levels were about 1 and 4 μg/ml at the two dietary concentrations. N-acetyl-2-aminofluorene induced hepatocellular preneoplastic lesions measured as hepatocellular altered foci expressing glutathione S-transferase-P, reflecting initiation. Induced foci were reduced with administration of both concentrations of acetaminophen. Acetaminophen by itself produced no DNA adducts nor did it alter the high formation of N-acetyl-2-aminofluorene–DNA adducts, about 200 in 10 8 nucleotides, measured by nucleotide postlabeling. Acetaminophen did not affect background liver cell proliferation, but significantly reduced N-acetyl-2-aminofluorene-induced increased proliferation measured by proliferating cell nuclear antigen immunostaining. Thus, acetaminophen effectively protected hepatocytes from the initiating effects of N-acetyl-2-aminofluorene, possibly through a cytoprotective effect resulting from slowing the rate of induced cell turnover.
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第 3 章 – 四氯化碳毒性的化学机制
DOI：
10.1016/b978-0-12-566503-2.50010-0
发表时间：
1977
影响因子：
3.1
作者：
R. O. Recknagel;E. A. Glende;A. Hruszkewycz
通讯作者：
A. Hruszkewycz
四氯化碳的还原氧化：三氯甲基过氧自由基作为四氯化碳转化为亲电氯的可能中间体。
影响因子：
3.9
作者：
B. Mico;L. Pohl
通讯作者：
L. Pohl
DOI：
10.1016/s0021-9258(17)38535-6
发表时间：
1986-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
H. Connor;R. Thurman;M. Galizi;R. Mason
通讯作者：
H. Connor;R. Thurman;M. Galizi;R. Mason
完整肝细胞中药物代谢的调节因素。
影响因子：
21.1
作者：
R. Thurman;F. Kauffman
通讯作者：
F. Kauffman
使用脉冲辐射分解和高能辐射程序自旋捕获 CCI4 活化的自由基产物
影响因子：
3.5
作者：
A. Tomasi;E. Albano;K. Lott;T. Slater
通讯作者：
T. Slater