TY - JOUR
T1 - Oltipraz chemoprevention trial in Qidong, People's Republic of China
T2 - Unaltered oxidative biomarkers
AU - Glintborg, Bente
AU - Weimann, Allan
AU - Kensler, Thomas W.
AU - Poulsen, Henrik E.
N1 - Funding Information:
We thank the study team and the participants for their contributions to this project. This work was supported in part by NIH Grant ES06052.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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.
AB - 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.
KW - Aflatoxin
KW - Chemoprevention
KW - Free radicals
KW - Oltipraz
KW - Randomized clinical trial
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U2 - 10.1016/j.freeradbiomed.2006.06.015
DO - 10.1016/j.freeradbiomed.2006.06.015
M3 - Article
C2 - 16934685
AN - SCOPUS:33747339232
SN - 0891-5849
VL - 41
SP - 1010
EP - 1014
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -