Journal of the Korean Society of Tobacco Science (한국연초학회지)

The Korean Society of Tobacco Science (한국연초학회)
권호 표지

Toxicity Assessment of Gas Phase in Cigarette Smoke Using Cell-free Assay

  • Published : 2007.12.25
Download PDF
⟨ Previous Next ⟩

Abstract

In vitro toxicity tests such as cytotoxicity, mutagenicity and genotoxicity assay are useful for evaluating the relative toxicity of smoke or smoke condensates obtained from different cigarette configurations. A major disadvantage of these tests is relatively time-consuming, complicated and expensive. Recently, a cell-free glutathione consumption assay (GCA) as a rapid and simple screening method for the toxicity assessment of smoke has been reported by Cahours et al. (CORESTA, 2006). This study was carried out to assess the GCA application capable of predicting the toxicity of gas/vapor phase (GVP) of cigarette smoke and to identify individual compounds responsible for the glutathione (GSH) consumption in smoke. Each GVPs from 2R4F, standard cigarette, carbon filter cigarette (ExC) and new carbon filter cigarette (ExN), test cigarettes were collected by automatic smoking machine and evaluated the relative toxicity by GCA and neutral red uptake (NRU) assay. Toxic compounds existed in smoke were also chosen, relative toxicities of these compounds were screened by using two methods and compared individually. The overall order of toxicity by GCA was 2R4F > ExC > ExN, which was consistent with the result of Neutral Red Uptake assay. The levels of carbonyl compounds of ExN were lower than those of 2R4F and ExC, indicating that GSH consumption was associated with carbonyl compound yields. A major toxicant under current study is acrolein, which contributed to more than half of the GSH consumption. Collectively, the toxicity of GVP determined by GCA method may be mainly attributed to acrolein.

Keywords

References

  1. Andreoli, C., Gigante, D. and Nunziata, A. (2003) A review of in vitro methods to assess the biological activity of tobacco smoke with the aim of reducing the toxicity of smoke. Toxicol. In vitro 17: 587-594 https://doi.org/10.1016/S0887-2333(03)00091-2
  2. Aufderheide, M., Knebel, J,W. and Ritter, D. (2003) An improved in vitro model for testing the pulmonary toxicity of complex mixture such as cigarette smoke. Exp. Toxic. Pathol. 55: 51-57 https://doi.org/10.1078/0940-2993-00298
  3. Bombick, D. W. and Doolittle, D. J. (1995) The role of chemical structure and cell type in the cytotoxicity of low molecular weight aldehydes and pyridine. In Vitro Toxicol. 8: 349-356
  4. Cahours, X., Blanchet, M, Haond, C., Marchand V. and Dumery, B. (2006) A cell-free method to assess the gaseous phase cytotoxicity of cigarette smoke. Coresta Conference Paris, France 4
  5. Grafstrom, R. C, Willey, J, C., Sundqvist, K. and Harris, C. C. (1986) Pathobiological effects of tobacco smoke-related aldehydes in cultured humn bronchial epithelial cells. In Banury Report 23: Mechanisms in Tobacco Carcinogenesis (D. Hoffmann and C. C. Harris, Eels.), p273-285 Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
  6. Gurtoo, H. L., Marinello, A. J., Struck, R. F., Paul, B. and Dahms, R. P. (981) Studies on the mechanism of denaturation of cytochrome P-450 by cyclophosphamide and its metabolites. J. Biol. Chem. 256: 11691-11701
  7. Harris, C. C., Willey, J. C., Saladino, A. J., and Grafstrom, R. C. (1985) Effects of tumor promoters, aldehyde, peroxides and tobacco smoke condensate on growth and differentiation of cultured normal and transformed human bronchial cells. In Cancer of the Respiratory Tract: Predisposing Factors P. 159. Mass, et al., ds., Plenum Press, New York
  8. Heinz-Verner, H., Gerhard, G., Dinamis, J. and Gerhard, S. (2004) Mechanistically-based Tests for toxicity of tobacco smoke. Coresta Conference Kyoto, Japan 1-8
  9. INVITTOX (1990) The FRAME modified neutral red uptake cytotoxicity test. The ERGATT/FRAME data bank of in vitro techniques in toxicology, Protocol No. 3a, INVITTOX, Nottingham
  10. ISO Standard 3308 (2000) International Organization for Standardization. Routine analytical cigarette-smoking machine-Definitions and standard conditions. 4th ed
  11. Joshi, U. M., Kodavanti, P. R., and Mehendale, H. M. (1988) Glutathione metabolism and utilization of external thiols by cigarette smoke-challenged, isolated rat and rabbit lungs. Toxicol. Appl. Pharmacol. 96: 324-335 https://doi.org/10.1016/0041-008X(88)90091-9
  12. Kelly, F. J. (1999) Glutathione: in defence of lung. Food and chemical Toxieol. 37: 963-966 https://doi.org/10.1016/S0278-6915(99)00087-3
  13. Kode, A., Yang, S. R. and Rahman, I. (2006) Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells. Respir. Res. 7: 132 https://doi.org/10.1186/1465-9921-7-132
  14. Li, X. Y., Donaldson, K., Rahman, I., and MacNee, W. (1994) An investigation of the role of glutathione in the increased permeability induced by cigarette smoke in vivo and in vitro. Am. J. Respir. Crit. Care Med. 149: 1518-1525 https://doi.org/10.1164/ajrccm.149.6.8004308
  15. Marinello, A. J., Bansal, S. K., Paul, B., Koser, P. L., Love, J., Struck, R. F. and Gurtoo, H. L. (1984) Metabolism and binding of cyclophosphamide and its metabolite acrolein in rat hepatic microsomal cytochrome P450. Cancer Res. 44: 4615-4621
  16. Meacher, D. M. and Menzel, D. B. (1999) Glutathione depletion in lung cells by low molecular weight aldehydes. Cell Boil: & Toxicol. 15: 163-171 https://doi.org/10.1023/A:1007633519962
  17. NIH-National Institutes of Health (2001). Guidance document on using in vitro data to estimate in vivo starting doses for acute toxicity. Report of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program. Department of Health and Human Services, US Public Health Service, National Institutes of Health, Research Triangle Park, NC, NIH Publication NO. 01-4500
  18. Pouli, A. E., Hatzinikolaou, D. G., Piperi, C., Stavridou, A., Psallidopoulos, M. C. and Stavrides, J. C. (2003) The cytotoxic effect of volatile organic compounds of the gas phase of cigarette smoke on lung epithelial cells. Free Radic. Biol. Med. 34(3): 345-355 https://doi.org/10.1016/S0891-5849(02)01289-3
  19. Pryor, W. A. (1997) Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ, Health Perspect. 105: 875-882 https://doi.org/10.2307/3433297
  20. Putnam, K. P., Bombick, D. W. and Doolittle, D. J. (2002) Evaluation of eight in vitro assays for assessing the cytotoxicity of cigarette smoke condensate. Toxicol. In Vitro 16: 599-607 https://doi.org/10.1016/S0887-2333(02)00050-4
  21. Rahman, I., Li, X. Y., Donaldson, K., Harrison, D.J. and MacNee, W. (1995) Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. Am. J. Physiol. 269: L285-L292
  22. Rahman, I. and MacNee, W. (1999) Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease. Am. J. Physiol. Lung Cell Mol. Physiol. 277: Ll067-Ll088
  23. Ritter, D., Knebel, J. and Aufderheide, M. (2004) Comparative assessment of toxicities of mainstream smoke from commercial cigarettes. Inhal. Toxicol. 16: 1-10
  24. Reddy, S., Finkelstein, E. I., Wong, P. S., Phung, A., Cross, C. E. and van der Vliet, A. (2002) Identification of glutathione modifications by cigarette smoke. Free Radical Biol. Med. 33: 1490-1498 https://doi.org/10.1016/S0891-5849(02)01079-1
  25. Shin, H. J., Sohn, H. 0., Park, C. H., Lee, H. S., Min, Y. K. and Hyun, H. C. (2007) Evaluation of the in vitro biological activity of selected 35 chemicals. J. Kor. Soc. Tab. Sci. 29: 30-40
  26. Tewes F. J., Meisgen, T. J., Velter, D. J., Roemer, E. and Patskan, G. (2003) Toxicological evaluation of an electrically heated cigarette. Part 3: Genotoxicity and cytotoxicity of mainstream smoke. J. Appl. Toxicol. 23: 341-348 https://doi.org/10.1002/jat.925