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Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA–protein cross-links by liquid chromatography–tandem mass spectrometry

Archives of Toxicology volume 93, pages 763–773 (2019)Cite this article

Abstract

As a widespread industrial chemical, formaldehyde carcinogenicity has been highly controversial. Meanwhile, formaldehyde is an essential metabolite in all living cells. Previously, we have demonstrated exogenous formaldehyde causes DNA adducts in a nonlinear manner between 0.7 and 15.2 ppm using [13CD2]-formaldehyde for exposure coupled with the use of sensitive mass spectrometry. However, the responses from exposure to low doses of formaldehyde are still unknown. In this study, rats were exposed to 1, 30, and 300 ppb [13CD2]-formaldehyde for 28 days (6 h/day) by nose-only inhalation, followed by measuring DNA mono-adduct (N2-HOMe-dG) and DNA–protein crosslinks (dG-Me-Cys) as formaldehyde specific biomarkers. Both exogenous and endogenous DNA mono-adducts and dG-Me-Cys were examined with ultrasensitive nano-liquid chromatography–tandem mass spectrometry. Our data clearly show that endogenous adducts are present in all tissues analyzed, but exogenous adducts were not detectable in any tissue samples, including the most susceptible nasal epithelium. Moreover, formaldehyde exposure at 1, 30 and 300 ppb did not alter the levels of endogenous formaldehyde-induced DNA adducts or DNA–protein crosslinks. The novel findings from this study provide new data for risk assessment of exposure to low doses of formaldehyde.

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Abbreviations

FA:

Formaldehyde

dG:

Deoxyguanosine

DPCs:

DNA–protein crosslinks

HCD:

Higher-energy collisional dissociation

MS/MS:

Tandem mass spectrometry

PRM:

Parallel reaction monitoring

SRM:

Selected reaction monitoring

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Acknowledgements

We thank Dr. Leonard Collins for his assistance with HPLC purification and nano-UPLC–MS–MS. This project received funding from the American Chemistry Council and Formacare. The instrumentation was partially supported by funding from the NIEHS (R01ES024950 and P30ES010126). None of the funding agencies is involved in writing or have access to the manuscript before its submission.

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Authors and Affiliations

  1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Jiapeng Leng, Chih-Wei Liu, Hadley J. Hartwell, Rui Yu, Wanda M. Bodnar, Kun Lu & James A. Swenberg

  2. School of Chemical Engineering and Technology, North University of China, Taiyuan, 030051, Shanxi, China

    Jiapeng Leng

  3. Lovelace Respiratory Research Institute, Albuquerque, NM, 87108, USA

    Yongquan Lai

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  1. Jiapeng Leng
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  2. Chih-Wei Liu
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  3. Hadley J. Hartwell
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  4. Rui Yu
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  5. Yongquan Lai
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  6. Wanda M. Bodnar
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  7. Kun Lu
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  8. James A. Swenberg
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Correspondence to Kun Lu or James A. Swenberg.

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Leng, J., Liu, CW., Hartwell, H.J. et al. Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA–protein cross-links by liquid chromatography–tandem mass spectrometry. Arch Toxicol 93, 763–773 (2019). https://doi.org/10.1007/s00204-019-02393-x

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  • DOI: https://doi.org/10.1007/s00204-019-02393-x

Keywords

  • Formaldehyde
  • DNA damage
  • DNA adducts
  • DNA–protein crosslinks
  • Mass spectrometry