Mechanisms of mutagenesis by chloroacetaldehyde.

Author:

Jacobsen J S,Perkins C P,Callahan J T,Sambamurti K,Humayun M Z

Abstract

Abstract A number of bifunctional chemical mutagens induce exocyclic DNA lesions. For example, 2-chloroacetaldehyde (CAA), a metabolite of vinyl chloride, readily reacts with single-stranded DNA to predominantly form etheno lesions. Here, we report on in vivo mutagenesis caused by CAA treatment of DNA in vitro. These experiments used partially duplex phage M13AB28 replicative form DNA in which a part of the lacZ gene sequence was held in single-stranded form to direct reaction with CAA. CAA-treated partial duplex DNA was transfected into Escherichia coli, and the induced base changes were defined by DNA sequencing. These experiments suggested that CAA treatment induced mutations at cytosines, much less efficiently at adenines, but not at guanines or thymines. Among mutations targeted to cytosine, 80% were C-to-T transitions and 20% were C-to-A transversions. Application of a post-labeling method detected dose-dependent formation of ethenoadenine and ethenocytosine in CAA treated DNA. These data indicate that ethenocytosine is a highly efficient mutagen with properties suggestive of a non-instructional DNA lesion in vivo. Paradoxically, ethenoadenines are efficiently bypassed by a mechanism which appears to be largely nonmutagenic.

Publisher

Oxford University Press (OUP)

Subject

Genetics

Cited by 21 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Base Pairing and Miscoding Properties of 1,N6-Ethenoadenine- and 3,N4-Ethenocytosine-Containing RNA Oligonucleotides;Biochemistry;2013-03-07

2. Quantum Mechanical Calculations for the Misincorporation of Nucleotides Opposite Mutagenic 3,N4-Ethenocytosine;The Journal of Physical Chemistry B;2012-08-31

3. Chloroacetaldehydes;Ullmann's Encyclopedia of Industrial Chemistry;2007-07-15

4. Escherichia coli DNA polymerase II can efficiently bypass 3,N4-ethenocytosine lesions in vitro and in vivo;Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis;2006-01

5. DNA damage and mutations produced by chloroacetaldehyde in a CpG-methylated target gene;Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis;2004-12

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