Huang C Y, Wilson M W, Lay L T, Chow C K, Robertson L W, Glauert H P
University of Kentucky, Department of Nutrition and Food Science, Lexington, 40506-0054.
Cancer Lett. 1994 Dec 9;87(2):223-8. doi: 10.1016/0304-3835(94)90226-7.
In this study we examined the ability of peroxisome proliferators to induce oxidative DNA damage in the form of 8-hydroxydeoxyguanosine (OHdG). We studied the hypolipidemic drug ciprofibrate, which is among the most potent and efficacious of the peroxisome proliferators, and perfluorodecanoic acid (PFDA), which is an inhibitor of peroxisomal beta-oxidation. Rats were fed 0.01% ciprofibrate in the diet, or were injected with PFDA at doses of 3 or 10 mg/kg every 14 days (controls and ciprofibrate-fed rats were given equivalent doses of corn oil). Rats were maintained for 10 days, 24 days, 6 weeks, 26 weeks, or 54 weeks. DNA was isolated from the liver at these times and hydrolysed to nucleosides, and the levels of OHdG as well as normal nucleosides were analysed by high-performance liquid chromatography with electrochemical detection. Ciprofibrate increased OHdG concentrations at all times except for the initial 10-day timepoint. Both doses of PFDA increased OHdG levels at all times except the last timepoint, at which only the higher dose produced a significant increase. This study shows that both ciprofibrate and PFDA induce oxidative DNA damage in the form of OHdG. Furthermore, the inhibition of peroxisomal beta-oxidation by PFDA does not affect the development of OHdG.
在本研究中，我们检测了过氧化物酶体增殖剂以8-羟基脱氧鸟苷（OHdG）形式诱导氧化性DNA损伤的能力。我们研究了降血脂药物环丙贝特（它是效力最强且最有效的过氧化物酶体增殖剂之一）和全氟癸酸（PFDA，一种过氧化物酶体β氧化的抑制剂）。给大鼠喂食含0.01%环丙贝特的饲料，或者每14天注射剂量为3或10 mg/kg的PFDA（给对照组和喂食环丙贝特的大鼠注射等量的玉米油）。将大鼠饲养10天、24天、6周、26周或54周。在这些时间点从肝脏中分离DNA并水解为核苷，通过高效液相色谱电化学检测法分析OHdG以及正常核苷的水平。除了最初的10天时间点外，环丙贝特在所有时间点均增加了OHdG的浓度。两种剂量的PFDA在所有时间点均增加了OHdG水平，但在最后一个时间点除外，此时只有较高剂量产生了显著增加。本研究表明，环丙贝特和PFDA均以OHdG的形式诱导氧化性DNA损伤。此外，PFDA对过氧化物酶体β氧化的抑制作用并不影响OHdG的形成。
