Genotoxic Pyrrolizidine Alkaloids - Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

被引：62

作者：

Fu, Peter P. ^{[1
]}

Xia, Qingsu ^{[1
]}

Lin, Ge ^{[2
]}

Chou, Ming W. ^{[1
]}

机构：

[1] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

[2] Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2002年 / 3卷 / 09期

关键词：

Pyrrolizidine alkaloids; tumorigenicity; riddelliine; DNA adducts; genotoxic mechanism;

D O I：

10.3390/i3090948

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：

Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecine-type pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed.

引用

页码：948 / 964

页数：17

共 75 条

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