Identification of a N7-guanine adduct of 1-bromopropane in calf thymus DNA by mass spectrometry

Pritam Thapa; Eun-Kyung Kim; Mahesh Raj Nepal; Ki Sun Jeong; Mi Jeong Kang; Keumhan Noh; Sangkyu Lee; Hye Gwang Jeong; Jun-Ho Lee; Tae Cheon Jeong; Eung-Seok Lee

doi:10.1007/s13273-016-0002-5

Molecular & Cellular Toxicology

March 2016, Volume 12, Issue 1, pp 7–14

Identification of a N⁷-guanine adduct of 1-bromopropane in calf thymus DNA by mass spectrometry

Authors
Authors and affiliations

Pritam Thapa
Eun-Kyung Kim
Mahesh Raj Nepal
Ki Sun Jeong
Mi Jeong Kang
Keumhan Noh
Sangkyu Lee
Hye Gwang Jeong
Jun-Ho Lee
Tae Cheon JeongEmail author
Eung-Seok LeeEmail author

Original Paper

First Online:: 01 April 2016

Received:: 30 October 2015
Accepted:: 12 January 2016

DOI: 10.1007/s13273-016-0002-5

Cite this article as:: Thapa, P., Kim, EK., Nepal, M.R. et al. Mol. Cell. Toxicol. (2016) 12: 7. doi:10.1007/s13273-016-0002-5

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Abstract

As a replacement for chlorofluorocarbons that cause ozone depletion, 1-bromopropane has been widely used in work place. In the present study, the formation of N⁷-guanine adduct in DNA by 1-bromopropane was evaluated in vitro to elucidate the possible mechanism of its toxic action. N⁷-Propyl guanine was chemically synthesized and structurally characterized by NMR, UV, HPLC, and liquid chromatographyelectrospray ionization mass spectrometry (LC- ESI MS) for using as a reference standard. An incubation of 2ʹ-deoxyguanosine with 1-bromopropane produced N⁷-propyl adduct, which was identified by UV, HPLC and ESI-MS. In addition, N7-guanine adduct was also identified from the incorporation of calf thymus DNA with 1-bromopropane at the physiological condition by LC-ESI MS. Furthermore, the production of adduct was proportional to the amounts of 1-bromopropane used. These results indicated that the molecular mechanism underlying toxic effects of 1-bromopropane would be associated with the adduct formation on DNA at least in part.

Keywords

1-Bromopropane N⁷-Propyl guanine In vitro Calf thymus DNA Adduct formation

References

1.
Takeuchi, Y., Ichihara, G. & Kamijima, M. A review on toxicity of 2-bromopropane: mainly on its reproductive toxicity. J Occup Health 39:179–191 (1997).CrossRefGoogle Scholar
2.
Kim, Y. et al. Hematopoietic and reproductive hazards o Korean electronic workers exposed to solvents containing 2-bromopropane. Scand J Work Environ Health 39:387–391 (1996).CrossRefGoogle Scholar
3.
Park, J. S. et al. An outbreak of hematopoietic and reproductive disorders due to solvents containing 2-bromopropane in an electronic factory South Korea: epidemiological survey. J Occup Health 39:138–143 (1997).CrossRefGoogle Scholar
4.
Yu, I. J. et al. The occupational exposure level (OEL) for 2-bromopropane: the first OEL established by Korea. Appl Occup Environ Hyg 14:356–358 (1999).CrossRefPubMedGoogle Scholar
5.
Maeng, S. H. & Yu, I. J. Mutagenicity of 2-bromopropane. Ind Health 35:87–95 (1997).CrossRefPubMedGoogle Scholar
6.
Ichihara, G. Neuro-reproductive toxicities of 1-bromopropane and 2-bromopropane. Int Arch Occup Environ Health 78:79–96 (2005).CrossRefPubMedGoogle Scholar
7.
Barber, E. D., Donish, W. H. & Mueller, K. R. A procedure for the quantitative measurement of the mutagenicity of volatile liquids in th Ames Salmonella/ microsome assay. Mutat Res 90:31–48 (1981).CrossRefPubMedGoogle Scholar
8.
Lee, S. K. et al. Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice. J Appl Toxicol 27:358–367 (2007).CrossRefPubMedGoogle Scholar
9.
Sekiguchi, S., Suda, M., Zhai, Y. L. & Honma, T. Effects of 1-bromopropane, 2-bromopropane, and 1,2-dichloropropane on the estrous cycle and ovulation in F344 rats. Toxicol Lett 126:41–49 (2002).CrossRefPubMedGoogle Scholar
10.
Zhao, L. X. et al. Synthesis, characterization and in vitro identification of N7-guanine adduct of 2-bromopropane. Arch Pharm Res 25:39–44 (2002).CrossRefPubMedGoogle Scholar
11.
Yu, X. et al. Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons. Environ Res 85:48–52 (2001).CrossRefPubMedGoogle Scholar
12.
Thapa, P. et al. Depurination of dA and dG induced by 2-bromopropane at the physiological condition. J Appl Pharmacol 15:224–229 (2007).CrossRefGoogle Scholar
13.
Sherchan, J., Choi, H. & Lee, E. S. Depurination of nucleosides and calf thymus DNA induced by 2-bromopropane at the physiological condition. Bull Korean Chem Soc 30:2309–2317 (2009).CrossRefGoogle Scholar
14.
Lee, S. K. et al. Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male ICR mice. Arch Pharm Res 28:1177–1182 (2005).CrossRefPubMedGoogle Scholar
15.
Han, E. H. et al. 1-Bromopropane up-regulates cyclooxygenase-2 expression via NF-κB and C/EBP activation in murine macrophages. Food Chem Toxicol 50:1616–1622 (2012).CrossRefPubMedGoogle Scholar
16.
Kim, D. H. & Guengerich, F. P. Formation of the DNA adduct S-[2-(N7-guanyl)ethyl]glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione S-transferase levels and lack of a role for sulfation. Carcinogenesis 11:419–424 (1990).CrossRefPubMedGoogle Scholar
17.
Kim, D. H., Humphreys, W. G. & Guengerich, F. P. Characterization of S-[2-(N1-adenyl)ethyl]glutathione as an adduct formed in RNA and DNA from 1,2-dibromoethane. Chem Res Toxicol 3:587–594 (1990).CrossRefPubMedGoogle Scholar

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Authors and Affiliations

Pritam Thapa
- 1
Eun-Kyung Kim
- 1
Mahesh Raj Nepal
- 1
Ki Sun Jeong
- 1
Mi Jeong Kang
- 1
Keumhan Noh
- 1
Sangkyu Lee
- 2
Hye Gwang Jeong
- 3
Jun-Ho Lee
- 4
Tae Cheon Jeong
- 1
Email author
Eung-Seok Lee
- 1
Email author

Identification of a N⁷-guanine adduct of 1-bromopropane in calf thymus DNA by mass spectrometry

Abstract

Keywords

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