Abstract
Chloroethanes are widely produced and utilized compounds and have extensive human exposure. All of them are recognized as being toxic causing damage to the major parenchymous tissues, such as liver, kidney and central nervous system1. Some of them exert mutagenic activity in short-term tests in vitro but their carcinogenicity has not always been adequately evidenced2,3. These compounds require bioactivation to the proximate toxin or carcinogen via metabolism by cytochrome P450-dependent enzymatic systems forming adducts with the genetic material. In some instances, metabolism results in detoxication or inactivation of the bioactive metabolite to innocuous compound, generally through conjugation with GSH4. The aim of this study is to better identify the genotoxic activity of chloroethanes in in vivo and in vitro systems, also in an attempt to validate a cell-free system as a short-term test for carcinogenicity prediction of initiating compounds, and to find structure-activity relationships among compounds belonging to the same chemical class.
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References
T. R. Torkelson, and V. K. Rowe, Halogenated haliphatic hydrocarbons, in: “Patty’s Industrial Hygiene and Toxicology, G. D. Clayton, ed., John Wiley & sons, Inc., New York, vol. 2 part B (1981).
IARC, Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 20, “Some Halogenated Hydrocarbons,” International Agency for Research on Cancer, Lyon, (1979).
IARC, Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 41, “Some Halogenated Hydrocarbons and Pesticide Exposure,” International Agency for Research on Cancer, Lyon, (1986).
T. L. MacDonald, Chemical mechanism of halocarbon metabolism, CRC Critical Reviews in Toxicology 11: 85 (1983).
G. Arfellini, S. Bartoli, A. Colacci, M. Mazzullo, M. C. Galli, G. Prodi, and S. Grilli, In vivo and in vitro binding of 1,2-dibromoethane and 1,2-dichloroethane to macromolecules in rat and mouse organs, J. Cancer Res. Clin. Oncol. 108:204 (1984).
A. Colacci, G. Arfellini, M. Mazzullo, G. Prodi, and S. Grilli, In vitro microsome-and cytosol-mediated binding of 1,2-dichloroethane and 1–2-dibromoethane with DNA, Cell Biol. Toxicol. 1:45 (1985).
A. Colacci, G. Arfellini, M. Mazzullo, G. Prodi, and S. Grilli, Genotoxicity of 1,1-dichloroethane, Res. Comm. Chem. Pathol. Pharmacol. 49: 243 (1985).
M. Mazzullo, A. Colacci, S. Grilli, G. Prodi, and G. Arfellini, 1,1,2-trichloroethane: evidence of genotoxicity from short-term tests, Jpn. J. Cancer Res. (Gann). 77: 532 (1986).
M. P. Turina, A. Colacci, S. Grilli, M. Mazzullo, G. Prodi, and G. Lattanzi, Short-term tests of genotoxicity for 1,1,1-trichloroethane, Res. Comm. Chem. Pathol. Pharmacol. 52: 305 (1986).
A. Colacci, S. Grilli, G. Lattanzi, G. Prodi, M. P. Turina, and M. Mazzullo, The covalent binding of 1,1,2,2-tetrachloroethane to macromolecules of rat and mouse organs, Teratoqen. Carcinoq. Mutagen. 7: 465 (1987).
G. Lattanzi, A. Colacci, S. Grilli, M. Mazzullo, G. Prodi, and M. P. Turina, Binding of hexachloroethane to biological macromolecules from rat and mouse organs, J. Toxicol. Environ. Health 24: 403 (1987).
M. P. Turina, A. Colacci, S. Grilli, M. Mazzullo, G. Prodi, G. Lattanzi, B. Sonora, S. Bartoli, and L. Guidotti, Metabolic activation and covalent binding to nucleic acids of penthachloroethane as short-term test of genotoxicity, Res. Comm. Chem. Pathol. Pharmacol. 63: 81 (1989).
W. K. Lutz, In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis, Mutat. Res. 65:289 (1979).
S. Parodi, M. Taningher, A. Zunino, L. Ottaggio, M. De Ferrari, and L. Santi, Quantitative predictivity of carcinogenicity for Sister Chromatid Exchanges in vivo, in: “Sister Chromatid Exchanges” part A, R. R. Tice and A. Hollaender, eds., Plenum Publishing Corporation, New York (1984).
G. H. Loew, M. Rebagliati, and M. Poulsen, Metabolism and relative carcinogenic potency of chloroethanes: a quantum chemical structure-activity study, Cancer Biochem. Biophys 7: 109 (1984).
H. A. Milman, D.L. Story, E. S. Riccio, A. Sivak, A. S. Tu, G. M. Williams, c. Tong, and C. A. Tyson, Rat liver foci and in vitro assays to detect initiating and promoting effects of chlorinated ethanes and ethylenes, Ann. N.Y. Acad. Sci. USA 534: 521 (1988).
N. R. Drinkwater, and J. J. Ginsler, Genetic control of hepatocarcinogenesis in C57BL/6J and C3H/HeJ imbred mice, Carcinoqenesis 7: 1701 (1986).
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Grilli, S. et al. (1991). Genotoxicity of Chloroethanes and Structure-Activity Relationships. In: Columbano, A., Feo, F., Pascale, R., Pani, P. (eds) Chemical Carcinogenesis 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3694-9_38
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DOI: https://doi.org/10.1007/978-1-4615-3694-9_38
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