Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkers.
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.
Glintborg
Bente
B
Department of Clinical Pharmacology Q7642, H:S Rigshospitalet, Tagensvej 20, Copenhagen, Denmark.
Weimann
Allan
A
Kensler
Thomas W
TW
Poulsen
Henrik E
HE
D016588:Anticarcinogenic Agents / Q000627:therapeutic use* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D002681:China; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010919:Placebos; D011719:Pyrazines / Q000627:therapeutic use* / Q000633:toxicity; D013871:Thiones; D013876:Thiophenes
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D010919:Placebos; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C024829:8-hydroxyguanine; D006147:Guanine; C026209:oltipraz; D004247:DNA