Evaluation for safety of antioxidant chemopreventive agents

被引:125
作者
Kawanishi, S [1 ]
Oikawa, S [1 ]
Murata, M [1 ]
机构
[1] Mie Univ, Dept Environm & Mol Med, Grad Sch Med, Tsu, Mie 5148507, Japan
关键词
D O I
10.1089/ars.2005.7.1728
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antioxidants are considered as the most promising chemopreventive agents against various human cancers. However, some antioxidants play paradoxical roles, acting as "double-edged sword." A primary property of effective and acceptable chemopreventive agents should be freedom from toxic effects in healthy population. Miscarriage of the intervention by P-carotene made us realize the necessity for evaluation of safety before recommending use of antioxidant supplements for chemoprevention. We have evaluated the safety of antioxidants on the basis of reactivity with DNA. Our results revealed that phytic acid, luteolin, and retinoic acid did not cause DNA damage under the experimental condition. Furthermore, phytic acid inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, in cultured cells treated with a H2O2-generating system. Thus, it is expected that these chemopreventive agents can safely protect humans against cancer. On the other hand, some chemopreventive agents with prooxidant properties (alpha-tocopherol, quercetin, catechins, isothiocyanates, N-acetylcysteine) caused DNA damage via generation of reactive oxygen species in the presence of metal ions and endogenous reductants: under some circumstances. Furthermore, other chemopreventive agents (beta-carotene, genistein, daidzein, propyl gallate, curcumin) exerted prooxidant properties after metabolic activation. Therefore, further studies on safety should be required when antioxidants are used for cancer prevention.
引用
收藏
页码:1728 / 1739
页数:12
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