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

Author： Fu Peter P.   Xia Qingsu   Lin Ge   Chou Ming W.  

Publisher： MDPI

E-ISSN： 1422-0067|3|9|948-964

ISSN： 1422-0067

Source： International Journal of Molecular Sciences, Vol.3, Iss.9, 2002-09, pp. : 948-964

Access to resources Favorite

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

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.

Related content

Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

By Ishino Kousuke   Kato Tatsuya   Kato Mamoru   Shibata Tatsuhiro   Watanabe Masatoshi   Wakabayashi Keiji   Nakagama Hitoshi   Totsuka Yukari  

International Journal of Molecular Sciences, Vol. 16, Iss. 2, 2015-02 ,pp. : 3474-3492 (19)

MDPI

Access to resources Recommend Favorite

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

By Yan Xinmiao   Kang Hong   Feng Jun   Yang Yiyan   Tang Kailin   Zhu Ruixin   Yang Li   Wang Zhengtao   Cao Zhiwei  

International Journal of Molecular Sciences, Vol. 17, Iss. 3, 2016-03 ,pp. : 318-318 (1)

MDPI

Access to resources Recommend Favorite

Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

By Skoneczny Dominik   Weston Paul A.   Zhu Xiaocheng   Gurr Geoff M.   Callaway Ragan M.   Weston Leslie A.  

International Journal of Molecular Sciences, Vol. 16, Iss. 11, 2015-11 ,pp. : 26721-26737 (17)

MDPI

Access to resources Recommend Favorite

Bromopyrrole Alkaloids with the Inhibitory Effects against the Biofilm Formation of Gram Negative Bacteria

By Sun Jingyuan   Wu Jiru   An Bang   Voogd Nicole J. de   Cheng Wei   Lin Wenhan  

Marine Drugs, Vol. 16, Iss. 1, 2018-01 ,pp. : 9-9 (1)

MDPI

Access to resources Recommend Favorite

Genotoxic Anti-Cancer Agents and Their Relationship to DNA Damage, Mitosis, and Checkpoint Adaptation in Proliferating Cancer Cells

By Swift Lucy H.   Golsteyn Roy M.  

International Journal of Molecular Sciences, Vol. 15, Iss. 3, 2014-02 ,pp. : 3403-3431 (29)

MDPI

Access to resources Recommend Favorite