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长期乙醇摄入对叙利亚金黄地鼠颊囊和肝脏中苯并(a)芘代谢及谷胱甘肽S-转移酶活性的影响。

Effects of chronic ethanol consumption on benzo(a)pyrene metabolism and glutathione S-transferase activities in Syrian golden hamster cheek pouch and liver.

作者信息

Murphy S E, Hecht S S

出版信息

Cancer Res. 1986 Jan;46(1):141-6.

PMID:3940187
Abstract

The metabolism of benzo(a)pyrene (BaP) by hepatic or cheek pouch epithelium microsomes obtained from Syrian golden hamsters which had been consuming an ethanol-containing liquid diet for 4 wk and from pair-fed controls was measured. Glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene or (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene as substrates was measured in cytosol obtained from the liver or cheek pouch epithelium of the same animals. Cytosolic hepatic glutathione levels were measured in both ethanol-consuming and control animals. The metabolism of BaP to 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene (BaP-4,5-diol), 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BaP-7,8-diol), 9-hydroxybenzo(a)pyrene (9-OH-BaP), and 3-hydroxybenzo(a)pyrene (3-OH-BaP) by hepatic microsomes from ethanol-consuming hamsters was significantly reduced (40-52%) (P less than 0.05) compared to control microsomes. However, a 2-fold increase (P less than 0.05) in the metabolism of BaP to BaP-7,8-diol and 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene was measured with microsomes from the cheek pouch epithelium of ethanol-consuming animals. There was no significant change in the production of BaP-4,5-diol, 9-OH-BaP, or 3-OH-BaP by cheek pouch epithelium microsomes of ethanol-consuming hamsters compared to controls. No difference in glutathione S-transferase activity of hepatic or cheek pouch epithelium cytosol between control and ethanol-consuming hamsters towards 1-chloro-2,4-dinitrobenzene or (+/-)-r-7,t-8-dihydroxy-t-9,10- epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was observed. Hepatic glutathione content was significantly (P less than 0.05) decreased after 2 wk (23%) and 4 wk (33%) of ethanol consumption. The results suggest a mechanism by which ethanol might enhance BaP tumorigenesis in the hamster cheek pouch.

摘要

对从食用含乙醇液体饲料4周的叙利亚金仓鼠以及配对喂食的对照仓鼠获得的肝微粒体或颊囊上皮微粒体中苯并(a)芘(BaP)的代谢进行了测定。以1-氯-2,4-二硝基苯或(+/-)-r-7,t-8-二羟基-t-9,10-环氧-7,8,9,10-四氢苯并(a)芘为底物,测定了从相同动物的肝脏或颊囊上皮获得的胞质溶胶中的谷胱甘肽S-转移酶活性。测定了食用乙醇的动物和对照动物肝脏中的胞质肝谷胱甘肽水平。与对照微粒体相比,食用乙醇的仓鼠肝微粒体将BaP代谢为4,5-二氢-4,5-二羟基苯并(a)芘(BaP-4,5-二醇)、7,8-二氢-7,8-二羟基苯并(a)芘(BaP-7,8-二醇)、9-羟基苯并(a)芘(9-OH-BaP)和3-羟基苯并(a)芘(3-OH-BaP)的能力显著降低(40 - 52%)(P < 0.05)。然而,在食用乙醇的动物的颊囊上皮微粒体中,测定到BaP代谢为BaP-7,8-二醇和9,10-二氢-9,10-二羟基苯并(a)芘的能力增加了2倍(P < 0.05)。与对照相比,食用乙醇的仓鼠颊囊上皮微粒体产生BaP-4,5-二醇、9-OH-BaP或3-OH-BaP的量没有显著变化。未观察到对照仓鼠和食用乙醇的仓鼠肝脏或颊囊上皮胞质溶胶对1-氯-2,4-二硝基苯或(+/-)-r-7,t-8-二羟基-t-9,10-环氧-7,8,9,10-四氢苯并(a)芘的谷胱甘肽S-转移酶活性存在差异。食用乙醇2周(23%)和4周(33%)后,肝脏谷胱甘肽含量显著降低(P < 0.05)。结果提示了乙醇可能增强仓鼠颊囊中BaP致癌作用的一种机制。

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