Comparative effects of butylated hydroxyanisole on hepatic in vivo DNA binding and in vitro biotransformation of aflatoxin B1 in the rat and mouse.
Comparative effects of butylated hydroxyanisole on hepatic in vivo DNA binding and in vitro biotransformation of aflatoxin B1 in the rat and mouse.
复制标题
丁基羟基苯甲醚对大鼠和小鼠肝脏体内 DNA 结合和黄曲霉毒素 B1 体外生物转化的影响比较。
DOI：
10.1016/0041-008x(87)90132-3
复制
发表时间：
1987
影响因子：
3.8
通讯作者：
Eaton,DL
中科院分区：
文献类型：
--
作者：
Monroe,DH;Eaton,DL
为了确定介导种属和处理相关的黄曲霉毒素B1（AFB）敏感性差异的机制，我们进行了一项比较研究，研究了饮食丁基羟基茴香醚（BHA）对大鼠和小鼠肝脏体内DNA结合和体外AFB生物转化的影响。小鼠对AFB的致癌作用具有抵抗力，BHA预处理已被证明可以抑制AFB在高度易感大鼠中的致癌作用。大鼠和小鼠喂食对照饲料或含有0.75%BHA的相同饲料10天。在第11天，一半的对照组和BHA动物通过腹腔注射给予[3 H]AFB（0.25 mg/kg的二甲基亚砜溶液）。2小时后处死动物，测定AFB与肝DNA的共价结合。处死剩余动物，制备用于体外试验的肝亚细胞组分。BHA治疗导致小鼠体内肝脏AFB-DNA加合物形成减少至对照组的68%，但在大鼠中，治疗使AFB-DNA结合减少至对照组的18%。此外，对照小鼠的肝脏AFB-DNA结合率仅为对照大鼠的1.2%。对照组小鼠体外AFB对环氧化物的激活率是对照组大鼠的3.4倍。BHA预处理使小鼠AFB活化增加3.3倍，但对大鼠氧化代谢无影响。与对照组大鼠相比，对照组小鼠对黄曲霉毒素B-环氧化物的谷胱甘肽S-转移酶（GST）活性高52倍，但对1-氯-2，4-二硝基苯（CDNB）的GST活性仅高2.6倍。在小鼠中，BHA没有显著增加GST对AFB-环氧化物的活性，但增加GST对CDNB的活性3.1倍。在大鼠中，BHA使GST对AFB-环氧化物和CDNB的活性分别增加了3.2倍和2.1倍。小鼠对对硝基环氧苯乙烯的环氧水解酶活性仅为大鼠的52%。BHA在小鼠和大鼠中分别使环氧化物水解酶活性增加3.8倍和2.5倍。这些数据表明，小鼠具有高水平的黄曲霉毒素B-环氧化物-特异性GST活性相对于大鼠。AFB-环氧化物的形成速率和环氧化物水解酶的活性在高GST活性的条件下似乎相对不重要，而GST活性升高，因此AFB-环氧化物的失活，似乎是种属和BHA诱导的AFB-DNA加合物形成差异的关键组分，并且可能是AFB肝癌性。
To determine the mechanisms which mediate species- and treatment-related differences in susceptibility to aflatoxin B1(AFB), we conducted a comparative study of the effects of dietary butylated hydroxyanisole (BHA) on the hepatic in vivo DNA binding and in vitro biotransformation of AFB in the rat and mouse. Mice are resistant to the hepatocarcinogenic effects of AFB, and BHA pretreatment has been shown to inhibit the carcinogenic effects of AFB in the highly susceptible rat. Rats and mice were fed a control diet or an identical diet containing 0.75% BHA for 10 days. On the 11th day, one-half of the control and BHA animals were administered [3H]AFB (0.25 mg/kg in dimethyl sulfoxide) via intraperitoneal injection. Animals were killed 2 hr later and covalent binding of AFB to hepatic DNA was determined. The remaining animals were killed for preparation of hepatic subcellular fractions used in in vitro assays. BHA treatment resulted in a decrease in in vivo hepatic AFB-DNA adduct formation in mice to 68% of control, but, in rats, treatment decreased AFB-DNA binding to 18% of control. Furthermore, hepatic AFB-DNA binding in control mice was only 1.2% of that measured in control rats. The rate of in vitro activation of AFB to the epoxide was 3.4-fold greater in control mice relative to control rats. BHA pretreatment increased the activation of AFB in mice 3.3-fold, but had no effect on oxidative metabolism in rats. Control mice had 52 times greater glutathione S-transferase (GST) activity toward the AFB-epoxide, but only 2.6 times greater GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB), compared to that of control rats. In mice, BHA did not significantly increase GST activity toward the AFB-epoxide, but increased GST activity toward CDNB 3.1-fold. In rats, BHA increased GST activity toward the AFB-epoxide and CDNB by 3.2- and 2.1-fold, respectively. Epoxide hydrolase activity toward p-nitrostyrene oxide in mice was only 52% of the activity in rats. BHA increased epoxide hydrolase activity 3.8- and 2.5-fold in mice and rats, respectively. These data indicate that mice have high levels of an AFB-epoxide-specific GST activity relative to that of the rat. The rate of formation of the AFB-epoxide and the activity of epoxide hydrolase appear to be relatively unimportant under conditions of high GST activity, whereas elevated GST activity, and thus inactivation of the AFB-epoxide, appears to be the critical component in species- and BHA-induced differences in AFB-DNA adduct formation and, presumably, AFB hepatocarcinogenicity.
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DOI：
10.3109/00498258709043924
发表时间：
1987
期刊：
Xenobiotica; the fate of foreign compounds in biological systems
影响因子：
--
作者：
Holeski,CJ;Eaton,DL;Monroe,DH;Bellamy,GM
通讯作者：
Bellamy,GM
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影响因子：
--
作者：
Hsieh,DP;Wong,JJ
通讯作者：
Wong,JJ
一种方便的环氧化物水合酶反相液相色谱测定方法。
影响因子：
2.9
作者：
R. Westkaemper;R. Hanzlik
通讯作者：
R. Hanzlik
饮食中给予 2(3)-t-丁基-4-羟基苯甲醚可提高小鼠肝微粒体介导的黄曲霉毒素 B1 的 DNA 结合和致突变性。
影响因子：
5.1
作者：
A. Rahimtula;M. Martin
通讯作者：
M. Martin
谷胱甘肽对黄曲霉毒素B1在大鼠体内的解毒作用。
DOI：
--
发表时间：
1979
期刊：
Xenobiotica; the fate of foreign compounds in biological systems
影响因子：
--
作者：
G. Emerole;N. Nešković;R. Dixon
通讯作者：
R. Dixon