Dehydromonocrotaline generates sequence-selective N-7 guanine alkylation and heat and alkali stable multiple fragment DNA crosslinks.

Abstract:

:Monocrotaline is a pyrrolizidine alkaloid known to cause toxicity in humans and animals. Its mechanism of biological action is still unclear although DNA crosslinking has been suggested to a play a role in its activity. In this study we found that an active metabolite of monocrotaline, dehydromonocrotaline (DHM), alkylates guanines at the N7 position of DNA with a preference for 5'-GG and 5'-GA sequences. In addition, it generates piperidine- and heat-resistant multiple DNA crosslinks, as confirmed by electrophoresis and electron microscopy. On the basis of these findings, we propose that DHM undergoes rapid polymerization to a structure which is able to crosslink several fragments of DNA.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Pereira TN,Webb RI,Reilly PE,Seawright AA,Prakash AS

doi

10.1093/nar/26.23.5441

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

5441-7

issue

23

eissn

0305-1048

issn

1362-4962

pii

gkb838

journal_volume

26

pub_type

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