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
. 2014 Apr 21;27(4):480-2.
doi: 10.1021/tx5000602. Epub 2014 Mar 26.

Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells

Vyom Sharma  1 , Leonard B Collins, Jean M Clement, Zhenfa Zhang, Jun Nakamura, James A Swenberg
Affiliations

Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells

Vyom Sharma et al. Chem Res Toxicol. .

Abstract

For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D3]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O(6)-methyl-dG adducts ≥1.8/10(8) dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Endogenous versus exogenous adducts in AHH-1 cells exposed to D3-MNU (0.0075 μM to 2.5 μM) for 1 h. The endogenous and exogenous O6-me-dG and N7-me-G adducts at each exposure concentration are plotted on a log versus log scale. Data represent the mean ± SD.
See this image and copyright information in PMC

References

    1. Hanahan D.; Weinberg R. A. (2000) The hallmarks of cancer. Cell 100, 57–70. - PubMed
    1. Swenberg J. A.; Fryar-Tita E.; Jeong Y. C.; Boysen G.; Starr T.; Walker V. E.; Albertini R. J. (2008) Biomarkers in toxicology and risk assessment: informing critical dose-response relationships. Chem. Res. Toxicol. 21, 253–265. - PubMed
    1. Swenberg J. A.; Lu K.; Moeller B. C.; Gao L.; Upton P. B.; Nakamura J.; Starr T. B. (2011) Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment. Toxicol. Sci. 120(Suppl 1), S130–S145. - PMC - PubMed
    1. National Research Council (2009) In Science and Decisions: Advancing Risk Assessment, National Academies Press, Washington, DC. - PubMed
    1. Doak S. H.; Jenkins G. J.; Johnson G. E.; Quick E.; Parry E. M.; Parry J. M. (2007) Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens. Cancer Res. 67, 3904–3911. - PubMed

Publication types

MeSH terms

LinkOut - more resources