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用苯并(a)芘处理的大鼠中DNA、蛋白质和抗氧化酶(超氧化物歧化酶和过氧化氢酶)的氧化应激。

Oxidative stress to DNA, protein, and antioxidant enzymes (superoxide dismutase and catalase) in rats treated with benzo(a)pyrene.

作者信息

Kim K B, Lee B M

机构信息

Division of Toxicology, School of Pharmacy, Sung Kyun Kwan University, Suwon, Kyunggi-Do, South Korea.

出版信息

Cancer Lett. 1997 Feb 26;113(1-2):205-12. doi: 10.1016/s0304-3835(97)04610-7.

Abstract

Oxidative DNA damage (as 8-hydroxydeoxyguanosine; 8-OHdG), carbonyl content of proteins, and activities of superoxide dismutase (SOD) and catalase were investigated in female Sprague-Dawley rats orally treated with benzo(a)pyrene (B(a)P) (75 mg/rat). HPLC-ECD system showed that B(a)P increased the level of 8-OHdG in tissues (liver, kidney, and lung), but a statistical significance was observed only in the liver (3.5-fold increase) and kidney (two-fold increase). In the liver, the peak level (21 +/- 5 8-OHdG residues/10(5) dG) was obtained 12 h after treatment and returned close to control level (9 +/- 2 8-OHdG residues/10(5) dG) at 24 h, but 8-OHdG was persistent in the kidney. Carbonyl contents measured as an index of protein oxidation were slightly increased (23-35%) in the cytosolic fraction of tissues, but a significant increase (2.19 nmol/mg protein, 35% increase) was observed only in the liver 6 h after treatment, similar to 8-OHdG. However, the rate of increase was relatively low compared to that of 8-OHdG. In contrast to DNA and protein damages, the activities of SOD and catalase in the tissues were decreased after treatment (P < 0.01) and gradually increased to control levels. SOD and catalase activities in organs of rats were inversely correlated with oxidative damages to DNA and protein. The data suggest that B(a)P oxidatively altered DNA, protein, and antioxidant enzymes in rats and this might be associated with B(a)P carcinogenesis.

摘要

在口服苯并(a)芘(B(a)P,75毫克/只大鼠)处理的雌性Sprague-Dawley大鼠中,研究了氧化DNA损伤(以8-羟基脱氧鸟苷;8-OHdG表示)、蛋白质羰基含量以及超氧化物歧化酶(SOD)和过氧化氢酶的活性。高效液相色谱-电化学检测系统显示,B(a)P增加了组织(肝脏、肾脏和肺)中8-OHdG的水平,但仅在肝脏(增加3.5倍)和肾脏(增加2倍)中观察到统计学意义。在肝脏中,处理后12小时达到峰值水平(21±5个8-OHdG残基/10⁵个dG),24小时时接近对照水平(9±2个8-OHdG残基/10⁵个dG),但8-OHdG在肾脏中持续存在。作为蛋白质氧化指标测定的羰基含量在组织的胞质部分略有增加(23%-35%),但仅在处理后6小时的肝脏中观察到显著增加(2.19纳摩尔/毫克蛋白质,增加35%),与8-OHdG相似。然而,与8-OHdG相比,增加速率相对较低。与DNA和蛋白质损伤相反,处理后组织中SOD和过氧化氢酶的活性降低(P<0.01),并逐渐增加至对照水平。大鼠器官中的SOD和过氧化氢酶活性与DNA和蛋白质的氧化损伤呈负相关。数据表明,B(a)P在大鼠中氧化改变了DNA、蛋白质和抗氧化酶,这可能与B(a)P致癌作用有关。

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