Glintborg Bente, Weimann Allan, Kensler Thomas W, Poulsen Henrik E
Department of Clinical Pharmacology Q7642, H:S Rigshospitalet, Tagensvej 20, Copenhagen, Denmark.
Free Radic Biol Med. 2006 Sep 15;41(6):1010-4. doi: 10.1016/j.freeradbiomed.2006.06.015. Epub 2006 Jul 4.
Aflatoxin, which leads to formation of carcinogen-DNA adducts as well as oxidized DNA, is a well-known risk factor for development of hepatocellular carcinoma. The aim of the present study was to investigate if the chemopreventive agent oltipraz had an effect on DNA oxidation measured as oxidized guanine derivatives in urine among healthy individuals living in a region of China at high risk of exposure to aflatoxin and development of hepatocellular carcinoma. Two hundred thirty-three healthy residents of Qidong, PRC, were randomized to 8 weeks treatment with placebo, oltipraz 125 mg daily, or oltipraz 500 mg weekly, with a subsequent 8-week follow-up period. Urine samples were collected as overnight voids. Samples collected 4 weeks into the treatment period and 6 weeks into the follow-up period were analyzed for oxidized guanine derivatives with a HPLC-MS/MS method. A repeated-measures analysis of variance showed no significant differences between the randomization groups regarding changes in oxidized guanine derivatives. In the present double-blind, randomized, placebo-controlled trial performed among healthy individuals, oltipraz had no major effect on oxidative DNA damage. Mechanisms other than prevention of oxidative DNA damage may be of higher importance when oltipraz is used as a chemopreventive agent in humans.
黄曲霉毒素可导致致癌物 - DNA加合物以及氧化型DNA的形成，是肝细胞癌发生的一个众所周知的风险因素。本研究的目的是调查在中国一个黄曲霉毒素暴露和肝细胞癌发生风险较高地区生活的健康个体中，化学预防剂奥替普拉是否对以尿中氧化鸟嘌呤衍生物衡量的DNA氧化有影响。233名中国启东的健康居民被随机分为三组，分别接受为期8周的安慰剂治疗、每日125毫克奥替普拉治疗或每周500毫克奥替普拉治疗，随后有一个8周的随访期。尿液样本收集的是过夜晨尿。对治疗期第4周和随访期第6周收集的样本采用高效液相色谱 - 串联质谱法分析氧化鸟嘌呤衍生物。重复测量方差分析显示，随机分组在氧化鸟嘌呤衍生物变化方面无显著差异。在本次针对健康个体进行的双盲、随机、安慰剂对照试验中，奥替普拉对氧化性DNA损伤没有重大影响。当奥替普拉用作人体化学预防剂时，除预防氧化性DNA损伤之外的其他机制可能更为重要。
