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Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung

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Abstract

A hydrophilic-interaction liquid chromatography–tandem mass spectrometry (HILIC–MS–MS) method was developed for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolites in mouse liver and lung. The limits of detection of all analytes were in the range 0.017–0.057 ng mL−1, and recovery ranged from 88.4–119.8 % with intra and inter-day precision in the range 0.89–6.03 % and 1.01–6.97 %, respectively. This simple and accurate method was used to evaluate the effect of chronic alcohol consumption on NNK bioactivation in mouse tissue. Time-course curves for NNK and its metabolites were generated, and the areas under the curves (AUCs) were compared. It was found that target tissues of NNK carcinogenesis in C57BL/6 mice contained high levels of α-hydroxylation metabolites of NNK and its carbonyl reduction metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The most pronounced effect of alcohol was to enhance α-hydroxylation of NNK in mouse lung and liver, which suggests that chronic alcohol consumption may increase the risk of carcinogenicity associated with NNK in mice.

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References

  1. Hecht, S. S., & Hoffmann, D. (1988). Carcinogenesis, 9, 875–884.

    Article  CAS  Google Scholar 

  2. Krishnan, S., Hvastkovs, E. G., Bajrami, B., Schenkmanb, J. B., & Rusling, J. F. (2009). Mol BioSyst, 5, 163–169.

    Article  CAS  Google Scholar 

  3. Jalas, J. R., Hecht, S. S., & Murphy, S. E. (2005). Chem Res Toxicol, 8, 95–106.

    Article  Google Scholar 

  4. Smith, T. J., Guo, Z., Guengerich, F. P., & Yang, C. S. (1996). Carcinogenesis, 17, 809–813.

    Article  CAS  Google Scholar 

  5. Yamazaki, H., Inui, Y., Yun, C. H., Guengerich, F. P., & Shimada, T. (1992). Carcinogenesis, 3, 1789–1794.

    Article  Google Scholar 

  6. Patten, C. J., Smith, T. J., Friesen, M. J., Tynes, R. E., Yang, C. S., & Murphy, S. E. (1997). Carcinogenesis, 18, 1623–1630.

    Article  CAS  Google Scholar 

  7. Schulze, J., Schläger, W., Wünsch, R., & Richter, E. (1996). Carcinogenesis, 17, 1093–1099.

    Article  CAS  Google Scholar 

  8. Richter, E., Engl, J., Friesenegger, S., & Tricker, A. R. (2009). Chem Res Toxicol, 22, 1008–1017.

    Article  CAS  Google Scholar 

  9. Xin, H. J., Xie, F. W., Deng, D., & Chin, J. (2000). Anal Chem, 28, 436–438.

    CAS  Google Scholar 

  10. Zhang, L. Y., Weddle, D. L., Thomas, P. E., Zheng, B. Y., Castonguay, A., Schuller, H., & Miller, M. S. (2000). Toxicol Sci, 56, 313–323.

    Article  CAS  Google Scholar 

  11. Yang, Y. Y., Yu, C., Zhou, M., Pang, N. N., Li, N., Nie, H. G., Liao, J., Bai, Y., & Liu, H. W. (2011). J Chromatogr A, 1218, 6505–6510.

    Article  CAS  Google Scholar 

  12. Yang, Y. Y., & Liu, H. W. (2012). In F. L. Marcos & C. R. Ortiz (Eds.), Tobacco: production, uses and health implications (pp. 45–65). New York: Nova Science Publishers, Inc.

    Google Scholar 

  13. Adams, J. D., Brunnemann, K. D., & Hoffmann, D. (1983). J Chromatogr, 25, 6347–6351.

    Google Scholar 

  14. CORESTA recommended method no. 63, CORESTA, French, (2005)

  15. Xiong, W., Hou, H., Jiang, X. Y., Tang, G. L., & Hu, Q. Y. (2010). Anal Chim Acta, 674, 71–78.

    Article  CAS  Google Scholar 

  16. Zhao, B. B., Wang, S., Wang, J., Lang, H. L., Sun, S. H., Mao, J., & Zhang, J. X. (2012). J Chromatogr B, 899, 103–108.

    Article  CAS  Google Scholar 

  17. Lee, H. L., Wang, C. Y., Lin, S., & Paul, D. (2007). Talanta, 73, 76–80.

    Article  Google Scholar 

  18. Lang, H. L., Wang, S., Zhang, Q. D., Zhao, B. B., Wang, L., Cao, B. J., Wang, J., Mao, J., & Zhang, J. X. (2013). Anal Bioanal Chem, 405, 2083–2089.

    Article  CAS  Google Scholar 

  19. Tsutsumi, M., Lasker, J. M., Shimizu, M., Rosman, A. S., & Lieber, C. S. (1989). Hepatology, 10, 437–446.

    Article  CAS  Google Scholar 

  20. Johansson, J., Ekstroem, G., Scholte, B., Puzycki, D., Joernvall, H., & Ingelman-Sundberg, M. (1988). Biochemistry, 27, 1925–1934.

    Article  CAS  Google Scholar 

  21. Tuyns, A. J. (1979). Cancer Res, 39, 2840–2843.

    CAS  Google Scholar 

  22. Rogers, A. E., & Conner, M. W. (1986). Adv Exp Med Biol, 206, 473–495.

    CAS  Google Scholar 

  23. Staretz, M. E., & Hecht, S. S. (1995). Cancer Res, 55, 5580–5588.

    CAS  Google Scholar 

  24. Zhou, X., D’Agostino, J., Xie, F., & Ding, X. X. (2012). J Pharmacol Exp Ther, 341, 233–241.

    Article  CAS  Google Scholar 

  25. Jorquera, R., Castonguay, A., & Schuller, H. M. (1992). Cancer Res, 52, 3273–3280.

    CAS  Google Scholar 

  26. Korte, J. E., Brennan, P., Henley, S. J., & Boffetta, P. (2002). Epidemiology, 155, 496–506.

    Article  Google Scholar 

  27. McCoy, G. D., Hecht, S. S., Katayama, S., & Wynder, E. L. (1981). Cancer Res, 41, 2849–2854.

    CAS  Google Scholar 

  28. Castonguay, A., Riverson, A., Trushin, N., Reinhardt, J., Spathopoulos, S., Weiss, C. J., Reiss, B., & Hecht, S. S. (1984). Cancer Res, 41, 2885–2890.

    Google Scholar 

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Acknowledgments

This work was supported by NSFC (Grant no. 21175153). The authors gratefully thank the “Animal Experimental Center of Zhengzhou University”.

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Authors and Affiliations

  1. Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, 450001, China

    Baojun Cao, Qidong Zhang, Junhui Liu, Mingfei Feng & Jianxun Zhang

  2. China Tobacco Guizhou industrial Co. Ltd, Guizhou, 550000, China

    Houwei Ji

  3. Nanjing cigarette factory of China tobacco Jiangsu industrial Co. Ltd, Nanjing, 210000, China

    Hailei Lang

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  1. Baojun Cao
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  2. Qidong Zhang
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  3. Houwei Ji
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  4. Junhui Liu
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  5. Hailei Lang
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  6. Mingfei Feng
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  7. Jianxun Zhang
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Correspondence to Jianxun Zhang.

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Cao, B., Zhang, Q., Ji, H. et al. Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung. Anal Bioanal Chem 406, 4465–4471 (2014). https://doi.org/10.1007/s00216-014-7851-3

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  • DOI: https://doi.org/10.1007/s00216-014-7851-3

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