Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 25;7(2):36.
doi: 10.3390/toxics7020036.

Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner

Ke Bian  1 , James C Delaney  2 , Xianhao Zhou  3 , Deyu Li  4
Affiliations
Review

Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner

Ke Bian et al. Toxics. .

Abstract

As described elsewhere in this Special Issue on biomarkers, much progress has been made in the detection of modified DNA within organisms at endogenous and exogenous levels of exposure to chemical species, including putative carcinogens and chemotherapeutic agents. Advances in the detection of damaged or unnatural bases have been able to provide correlations to support or refute hypotheses between the level of exposure to oxidative, alkylative, and other stresses, and the resulting DNA damage (lesion formation). However, such stresses can form a plethora of modified nucleobases, and it is therefore difficult to determine the individual contribution of a particular modification to alter a cell's genetic fate, as measured in the form of toxicity by stalled replication past the damage, by subsequent mutation, and by lesion repair. Chemical incorporation of a modification at a specific site within a vector (site-specific mutagenesis) has been a useful tool to deconvolute what types of damage quantified in biologically relevant systems may lead to toxicity and/or mutagenicity, thereby allowing researchers to focus on the most relevant biomarkers that may impact human health. Here, we will review a sampling of the DNA modifications that have been studied by shuttle vector techniques.

Keywords: DNA adduct bypass; DNA damage; DNA lesion; DNA repair; mutagenicity; mutational signature; mutational spectrum; replication block; shuttle vector technique; site-specific mutagenesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview of the shuttle vector-based methods for evaluating DNA biomarkers.
Figure 2
Figure 2
Structures of oxidative lesions.
Figure 3
Figure 3
Structures of alkyl modifications.
Figure 3
Figure 3
Structures of alkyl modifications.
Figure 4
Figure 4
Structures of bulky and crosslinked lesions.
Figure 5
Figure 5
Structures of other nucleotide analogs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hwa Yun B., Guo J., Bellamri M., Turesky R.J. DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans. Mass Spectrom. Rev. 2018:1–28. doi: 10.1002/mas.21570. - DOI - PMC - PubMed
    1. Delaney J.C., Essigmann J.M. Biological properties of single chemical-DNA adducts: A twenty year perspective. Chem. Res. Toxicol. 2008;21:232–252. doi: 10.1021/tx700292a. - DOI - PMC - PubMed
    1. Miller E.C. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. Cancer Res. 1978;38:1479–1496. - PubMed
    1. Yu Y., Wang P., Cui Y., Wang Y. Chemical Analysis of DNA Damage. Anal. Chem. 2018;90:556–576. doi: 10.1021/acs.analchem.7b04247. - DOI - PMC - PubMed
    1. You C., Wang Y. Mass Spectrometry-Based Quantitative Strategies for Assessing the Biological Consequences and Repair of DNA Adducts. Acc. Chem. Res. 2016;49:205–213. doi: 10.1021/acs.accounts.5b00437. - DOI - PMC - PubMed