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).
Recommended Citation
Coulombe, R.A., and W. K. Rieben (2003). Lack of Apparent Base Sequence Preference of Activated Pyrrolizidine Alkaloid Cross-Links with DNA, in Poisonous Plants and Related Toxins, (T. Acamovic, C.S. Stewart and T.W. Pennycott eds.) CAB International, London. pp. 26-31.
Comments
Originally published by CAB International. Limited preview available through remote link.