Modulation of azaserine-induced pancreatic foci by phenolic antioxidants in rats.
Modulation of azaserine-induced pancreatic foci by phenolic antioxidants in rats.
复制标题
酚类抗氧化剂对重氮丝氨酸诱导的大鼠胰腺病灶的调节。
DOI：
10.1093/jnci/72.6.1405
复制
发表时间：
1984
期刊：
影响因子：
--
通讯作者：
T. Kensler
中科院分区：
文献类型：
--
作者：
B. Roebuck;D. MacMillan;D. Bush;T. Kensler
研究了膳食酚类抗氧化剂丁基羟基茴香醚[（BHA）CAS：25013-16-5;（1，1-二甲基乙基）-4-甲氧基苯酚]和丁基羟基甲苯[（BHT）CAS：128-37-0; 2，6-二叔丁基对甲酚]对胰腺肿瘤发生的影响。对雄性LEW近交系大鼠每周一次注射30 mg氮杂卓[CAS：115-02-6;重氮乙酸（酯）丝氨酸]/kg体重，持续3周，并在整个实验开始和开始后阶段维持对照饲料或添加0.45% BHA或0.45% BHT的对照饲料。开始后4个月，定量检查胰腺组织切片的癌前病灶的数量和大小。BHT和BHA处理分别使每个胰腺的嗜酸性病灶数量减少了32%和48%，但对病灶大小没有影响。相比之下，嗜碱性病灶不受这些抗氧化剂的调节。在肝脏和胰腺中检查了一系列参与致癌物灭活并已知被抗氧化剂处理干扰的酶活性。肝脏葡萄糖-6-磷酸脱氢酶，谷胱甘肽还原酶，谷胱甘肽-S-转移酶的活性显着升高，而过氧化氢酶和超氧化物歧化酶活性不变。谷胱甘肽过氧化物酶活性降低。在胰腺中，仅谷胱甘肽过氧化物酶活性受到影响，并且在BHA和BHT处理组中均降低。尽管胰腺对这些抗氧化剂的酶诱导作用不敏感，但病灶的形态学分析表明，BHA和BHT对阿扎色林诱导的病灶具有化学预防作用。这种减少是否反映了起始抑制、起始后抑制或多种效应的组合尚不清楚。
Effects of the dietary phenolic antioxidants butylated hydroxyanisole [(BHA) CAS: 25013-16-5; (1,1-dimethylethyl)-4-methoxyphenol] and butylated hydroxytoluene [(BHT) CAS: 128-37-0; 2,6-di-tert-butyl-p-cresol] on pancreatic tumorigenesis were examined. Male LEW inbred rats were given injections of 30 mg azaserine [CAS: 115-02-6; diazoacetate (ester) serine] per kg body weight once a week for 3 weeks and maintained on either a control diet or 0.45% BHA- or 0.45% BHT-supplemented control diet throughout the initiation and post-initiation phases of the experiment. At 4 months post initiation, pancreatic tissue sections were quantitatively examined for the number and size of preneoplastic foci. BHT and BHA treatments reduced the number of acidophilic foci per pancreas by 32 and 48%, respectively, but were without effect on focal size. By contrast, basophilic foci were not subject to modulation by these antioxidants. A constellation of enzyme activities involved in carcinogen inactivation and known to be perturbed by antioxidant treatment was examined in liver and pancreas. The hepatic activities of glucose-6-phosphate dehydrogenase, glutathione reductase, and glutathione-S-transferases were markedly elevated while catalase and superoxide dismutase activities were unchanged. Glutathione peroxidase activity was diminished. In the pancreas, only glutathione peroxidase activity was affected, and it was reduced in both the BHA and BHT treatment groups. Although the pancreas is refractory to the enzyme inductive effects of these antioxidants, morphometric analysis of foci demonstrated chemoprevention by BHA and BHT of azaserine-induced foci. Whether this reduction reflected inhibition of an initiation, postinitiation , or a combination of effects was not known.