Title

Lack of Apparent Base Sequence Preference of Activated Pyrrolizidine Alkaloid Cross- Links with DNA

Document Type

Contribution to Book

Journal/Book Title/Conference

Poisonous Plants and Related Toxins

Editor

T. Acamovic, C.S. Stewart and T.W. Pennycott

Publisher

CAB International

Publication Date

2003

First Page

26

Last Page

31

Abstract

Upon ingestion, pyrrolizidine alkaloids (PAs) are oxidized by cytochromes P-450 (CYPs) to reactive, pyrrolic bifunctional electrophiles that readily cross-link DNA, a reputed event critical in PA-induced toxicity. Our laboratory has demonstrated that PAs from nearly equal proportions of both DNA interstrand and DNA-protein cross-links in vitro (Hincks et al., 1991), and that the cytotoxic, antimitotic and megalocytic activity of PAs correlate with cross-linking (Kim et al. 1993)... We have recently shown that actin is the major protein involved in cellular PA-induced DNA-protein cross-links (Coulombe et al., 1999). Dehydrosenecionine (DHSN) and dehydromonocrotaline (DHMO) have also been shown to inhibit amplification fo a segment of pBR322, implying that cross-linking by activated PAs is functionally significant (Kim et al., 1999).

Comments

Originally published by CAB International. Limited preview available through remote link.