DOI QR코드

DOI QR Code

Activation of Dihaloalkanes by Thiol-dependent Mechanisms

  • Guengerich, F. Peter (Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine)
  • Published : 2003.01.31

Abstract

Dihaloalkanes constitute an important group of chemicals because of their widespread use in industry and agriculture and their potential for causing toxicity and cancer. Chronic toxic effects are considered to depend upon bioactivation, either by oxidation or thiol conjugation. Considerable evidence links genotoxicity and cancer with glutathione conjugations reactions, and some aspects of the mechanisms have been clarified with 1,2-dihaloalkanes and dihalomethanes. Recently the DNA repair protein $O^6$-alkylguanine transferase has been shown to produce cytotoxicity and genotoxicity by mans of a thiol-dependent process with similarities to the glutathione reactions.

Keywords

References

  1. Abril, N., Luque-Romero, F. L., Prieto-Alamo, M.-J., Rafferty, J. A., Margison, G. P. and Pueyo, C. (1997) Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes. Carcinogenesis 18. 1883-1888. https://doi.org/10.1093/carcin/18.10.1883
  2. Abril, N., Luqueromero. F. L., Prieto-Alamo, M. J., Margison, G. P. and Pueyo, C. (1995) ogt alkyltransferase enhances dibromoalkane mutagenicity in excIsIon repair-deficient Escherichia coli K-12. Mol. Carcinogen. 12. 110-117. https://doi.org/10.1002/mc.2940120208
  3. Abril, N. and Margison, G. P. (1999) Mammalian cells expressing Escherichia coli $O^{6}$-alkylguanine-DNA alkyltransferases are hypersensitive to dibromoalkanes. Chem. Res. Toxicol. 12, 544-551. https://doi.org/10.1021/tx980250h
  4. Ahmed, A. E. and Anders, M. W. (1976) Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies. Drug Metab. Dispos. 4, 357-361.
  5. Ahmed, A. E.. Kubic, V. L. and Anders, M. W. (1977) Metabolism of haloforms to carbon monoxide. I. In vitro studies. Drug Metab. Dispos. 5, 198-204.
  6. Andersen, M. E., Clewell, H. J., III. Gargas, M. L., Smith, F. A. and Reitz, R. H. (1987) Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol. Appl. Pharmacol. 87, 185-205. https://doi.org/10.1016/0041-008X(87)90281-X
  7. Anderson, M. W. and Maronpot, R. R. (1993) Methylene chloride-induced tumorigenesis. Carcinogenesis 14, 787-788. https://doi.org/10.1093/carcin/14.5.787
  8. Armstrong, R. N. (1997) Glutathione transferases. In Biotransformation, Vol. 3, Comprehensive Toxicology (Guengerich, F. P., ed.) 307-327, Elsevier Science Ltd., Oxford.
  9. Ballering, L. A. P., Nivard, M. J. M. and Vogel, E. W. (1994) Mutation spectra of 1,2-dibromoethane, 1,2-dichloroethane and 1-bromo-2-chloroethane in excision repair proficient and repair deficient strains of Drosophila melanogaster. Carcinogenesis 15, 869-875. https://doi.org/10.1093/carcin/15.5.869
  10. Cmarik, J. L.. Humphreys, W. G., Bruner, K. L., Lloyd, R. S., Tibbetts, C. and Guengerich, F. P. (1992) Mutation spectrum and sequence alkylation selectivity resulting from modification of bacteriophage M13mp18 with S-(2-chloroethyl)glutathione. Evidence for a role of S-[2-($N^{7}$-guanyl)ethyl]glutathione as a mutagenic lesion formed from ethylene dibromide. J. Biol. Chem. 267, 6672-6679.
  11. DeMarini, D. M., Shelton, M. L.. Warren, S. H., Ross, T. M., Shim, J. Y., Richard, A. M. and Pegram, R. A. (1997) Glutathione S-transferase-mediated induction of GC $\rightarrow$ AT transitions by halomethanes in Salmonella. Environ. Mol. Mutagen. 30,440-447. https://doi.org/10.1002/(SICI)1098-2280(1997)30:4<440::AID-EM9>3.0.CO;2-M
  12. Fossett, N. G., Byrne. B. J., Thcker, A. B., Arbour-Reily, P., Chang, S. and Lee, W. R. (1995) Mutation spectrum of 2- chloroethyl methanesulfonate in Drosophila melanogaster premeiotic germ cells. Mutat. Res. 331, 213-224. https://doi.org/10.1016/0027-5107(95)00079-X
  13. Foster, P. L., Wilkinson, W. G., Miller, J. K., Sullivan, A. D. and Barnes, W. M. (1988) An analysis of the mutagenicity of 1,2- dibromoethane to Escherichia coli: influence of DNA repair activities and metabolic pathways. Mutat. Res. 194, 171-181.
  14. Graminski, G. F., Kubo, Y. and Armstrong, R. N. (1989) Spectroscopic and kinetic evidence for the thiolate anion of glutathione at the active site of glutathione S-transferase. Biochemistry 28, 3562-3568. https://doi.org/10.1021/bi00434a062
  15. Graves, R. J., Coutts, C. and Green, T. (1995) Methylene chloride-induced DNA damage: an interspecies comparison. Carcinogenesis 16, 1919-1926. https://doi.org/10.1093/carcin/16.8.1919
  16. Green, T. (1983) The metabolic activation of dichloromethane and chlorofluoromethane in a bacterial mutation assay using Salmonella typhimurium. Mutat. Res. 118, 277-288. https://doi.org/10.1016/0165-1218(83)90211-2
  17. Guengerich, F. P., Crawford, W. M., Jr., Domoradzki, J. Y., Macdonald, T. L. and Watanabe, P. G. (1980) In vitro activation of 1,2-dichloroethane by microsomal and cytosolic enzymes. Toxicol. Appl. Pharmacol. 55, 303-317. https://doi.org/10.1016/0041-008X(80)90092-7
  18. Hashrni, M., Dechert, S., Dekant, W. and Anders, M. W. (1994) Bioactivation of $\left[13_{C} \right]$dichloromethane in mouse, rat, and human liver cytosol: $13_{C}$ nuclear magnetic resonance spectroscopic studies. Chem. Res. Toxicol. 7, 291-296. https://doi.org/10.1021/tx00039a004
  19. Huff, J., Bucher, J. and Barrett, J. C. (1996) Methylene chloride. Science 272, 1083-1084. https://doi.org/10.1126/science.272.5265.1083
  20. Humphreys, W. G., Kim, D. H. and Guengerich, F. P. (1991) Isolation and characterization of $N^{7}$ -guanyl adducts derived from 1,2-dibromo-3-chloropropane. Chern. Res. Toxicol. 4, 445-453. https://doi.org/10.1021/tx00022a008
  21. Humphreys, W. G., Kim, D.-H., Cmarik, J. L., Shimada, T. and Guengerich, F. P. (1990) Comparison of the DNA alkylating properties and mutagenic responses caused by a series of S-(2- haloethyl)-substituted cysteine and glutathione derivatives. Biochemistry 29, 10342-10350. https://doi.org/10.1021/bi00497a008
  22. Inskeep, P. B. and Guengerich, F. P. (1984) Glutathione-mediated binding of dibromoalkanes to DNA: specificity of rat glutathione S-transferases and dibromoalkane structure. Carcinogenesis 5, 805-808. https://doi.org/10.1093/carcin/5.6.805
  23. Inskeep, P. B., Koga, N., Cmarik, J. L. and Guengerich, F. P. (1986) Covalent binding of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct, S-[2-($N^{7}$- guanyl)ethyljglutathione. Cancer Res. 46, 2839-2844.
  24. Karran, P., Lindahl, T. and Griffin, B. (1979) Adaptive response to alkylating agents involves alteration in situ of $O^{6}$-methylguanine residues in DNA. Nature 280, 76-77. https://doi.org/10.1038/280076a0
  25. Kayser, M. F. and Vuilleumier, S. (2001) Dehalogenation of dichloromethane by dichloromethane dehalogenase/glutathione S-transferase leads to formation of DNA adducts. J. Bacteriol. 183, 5209-5212. https://doi.org/10.1128/JB.183.17.5209-5212.2001
  26. Kim, D. H. and Guengerich, F. P. (1989) Excretion of the mercapturic acid S-[2-($N^{7}$-guanyl)ethyl]-N-acetylcysteine in urine following administration of ethylene dibromide to rats. Cancer Res. 49, 5843-5851.
  27. Kim, D.-H., Humphreys, W. G. and Guengerich, F. P. (1990) Characterization of S-[2-($N^{1}$-adenyl)ethyl]glutathione formed in DNA and RNA from 1,2-dibromoethane. Chem. Res. Toxicol. 3, 587-594. https://doi.org/10.1021/tx00018a015
  28. Kim, M.-S. and Guengerich, F. P. (1997) Synthesis of oligonucleotides containing the ethylene dibromide-derived DNA adducts S-[2-($N^{7}$ -guanyl)ethyl]glutathione, S-[2-($N^{2}$-guanyl) ethyljglutathione, and S-[2-( $O^{6}$ -guanyl)ethyljglutathione at a single site. Chem. Res. Toxicol. 10, 1133-1143. https://doi.org/10.1021/tx9701081
  29. Kim, M.-S. and Guengerich, F. P. (1998) Polymerase blockage and misincorporation of dNTPs opposite the ethylene dibromide- derived DNA adducts S-[2-($N^{7}$-guanyl)ethyljglutathione, S-[2- ($N^{2}$-guanyl)ethyl]glutathione, and S-[2-($O^{6}$-guanyl)ethyl] glutathione. Chem. Res. Toxicol. 11, 311-316. https://doi.org/10.1021/tx970206m
  30. Koga, N., Inskeep, P. B., Harris, T. M. and Guengerich, F. P. (1986) S-[2-($N^{7}$-Guanyl)ethyljglutathione, the major DNA adduct formed from 1,2-dibromoethane. Biochemistry 25, 2192-2198. https://doi.org/10.1021/bi00356a051
  31. Letz, G. A, Pond, S. M., Osterloh, J. D., Wade, R. L. and Becker, C. E. (1984) Two fatalities after acute occupational exposure to ethylene dibromide. J. Am. Med. Assoc. 252, 2428-2431. https://doi.org/10.1001/jama.252.17.2428
  32. Liu, L., Pegg, A. E., Williams, K. M. and Guengerich, F. P. (2002) Paradoxical enhancement of the toxicity of 1,2- dibromoethane by $O^{6}$-alkylguanine-DNA alkyltransferase. J. BioI. Chem 277, 37920-37928. https://doi.org/10.1074/jbc.M205548200
  33. Marsch, G. A, Mundkowski, R G., Morris, B. J., Manier, M. L., Hartman, M. K. and Guengerich, F. P. (2001) Characterization of nucleoside and DNA adducts formed by S-(1-acetoxymethyl) glutathione and implications for dihalomethane-glutathione conjugates. Chem. Res. Toxicol. 14, 600-608. https://doi.org/10.1021/tx010006h
  34. Moshinsky, D. J. and Wogan, G. N. (1997) UV-induced mutagenesis of human p53 in a vector replicated in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 94, 2266-2271. https://doi.org/10.1073/pnas.94.6.2266
  35. Oda, Y., Yamazaki, H., T.hier, R, Ketterer, B., Guengerich, F. P. and Shimada, T. (1996) A new Salmonella typhimurium NM5004 strain expressing rat glutathione S-transferae 5-5: use in detection of genotoxicity of dihaloalkanes using an SOS/ umu test system. Carcinogenesis 17, 297-302.
  36. Ozawa, N. and Guengerich, F. P. (1983) Evidence for formation of an S-[2-($N^{7}$-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of 1,2-dibromoethane to DNA Proc. Natl. Acad. Sci. USA 80, 5266-5270. https://doi.org/10.1073/pnas.80.17.5266
  37. Pegram, R. A, Andersen, M. E., Warren, S. H., Ross, T. M. and Claxton, L. D. (1997) Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: contrasting results with bromodichloromethane and chloroform. Toxicol. Appl. Phannacol. 144, 183-188. https://doi.org/10.1006/taap.1997.8123
  38. Peterson, L. A, Harris, T. M. and Guengerich, F. P. (1988) Evidence for an episulfonium ion intermediate in the formation of S-[2-($N^{7}$-guanyl)ethyl]glutathione in DNA. J. Am. Chem. Soc. 110, 3284-3291. https://doi.org/10.1021/ja00218a045
  39. Rannug, U. and Beije, B. (1979) The mutagenic effect of 1,2- dichloroethane on Salmonella typhimurium. II. Activation by the isolated perfused rat liver. Chem.-Biol. Interact. 24, 265-285. https://doi.org/10.1016/0009-2797(79)90077-2
  40. Rannug, U., Sundvall, A and Ramel, C. (1978) The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium. I. Activation through conjugation with glutathione in vitro. Chem.-Biol. Interact. 20, 1-16. https://doi.org/10.1016/0009-2797(78)90076-5
  41. Reitz, R H., Mendrala, A. and Guengerich, F. P. (1989) In vitro metabolism of methylene chloride in human and animal tissues: use in physiologically-based pharmacokinetic models. Toxicol. Appl. Phannacol. 97, 230-246. https://doi.org/10.1016/0041-008X(89)90328-1
  42. Rhomberg, L. (1995) Use of quantitative modelling in methylene chloride risk assessment. Toxicology 102, 95-114. https://doi.org/10.1016/0300-483X(95)03039-I
  43. Sagher, D. and Strauss, B. (1983) Insertion of nucleotides opposite apurinic/apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis: uniqueness of adenine nucleotides. Biochemistry 22, 4518-4526. https://doi.org/10.1021/bi00288a026
  44. Sun, M. (1984) EDB contamination kindles federal action. Science 223, 464-466. https://doi.org/10.1126/science.6362008
  45. Thier, R., Mulier, M., Taylor, J. B., Pemble, S. E., Ketterer, B. and Guengerich, F. P. (1995) Enhancement of bacterial mutagenicity of bifunctional alkylating agents by expression of mammalian glutathione S-transferase. Chem. Res. Toxicol. 8, 465-472. https://doi.org/10.1021/tx00045a019
  46. Thier, R., Pemble, S. E., Taylor, J. B., Humphreys, W. G., Persmark, M., Ketterer, B. and Guengerich, F. P. (1993) Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes. Proc. Natl. Acad. Sci. USA 90, 8576-8580. https://doi.org/10.1073/pnas.90.18.8576
  47. Thier, R., Pemble, S., Kramer, H., Taylor, J. B., Guengerich, F. P., and Ketterer, B. (1996) Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane, and 1,2,3,4-diepoxybutane in Salmonella typhimurium. Carcinogenesis 17, 163-166. https://doi.org/10.1093/carcin/17.1.163
  48. van Bladeren, P. J., Breimer, D. D., Rotteveel-Smijs, G. M. T. and Moho, G. R. (1980) Mutagenic activation of dibromomethane and diiodomethane by mammalian microsomes and glutathione S-transferases. Mutat. Res. 74, 341-346. https://doi.org/10.1016/0165-1161(80)90192-2
  49. van Bladeren. P. J., van der Gen, A., Breimer, D. D. and Mohn, G. R. (1979) Stereoselective activation of vicinal dihalogen compounds to mutagens by glutathione conjugation. Biochem. Pharmacol. 28, 2521-2524. https://doi.org/10.1016/0006-2952(79)90019-4
  50. Wheeler, J. B., Stourman, N. V., Armstrong, R. N. and Guengerich, F. P. (2001 a) Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and vicinal dehaloethanes. Chem. Res. Toxicol. 14, 1107-1117. https://doi.org/10.1021/tx0100183
  51. Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N. and Guengerich, F. P. (2001b) Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and dihalomethanes. Chem. Res. Toxicol. 14, 1118-1127. https://doi.org/10.1021/tx010019v

Cited by

  1. Three common pathways of nephrotoxicity induced by halogenated alkenes vol.31, pp.1, 2015, https://doi.org/10.1007/s10565-015-9293-x
  2. Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard vol.29, pp.8, 2009, https://doi.org/10.1002/jat.1451
  3. Oxidative stress after sulfur mustard intoxication and its reduction by melatonin: efficacy of antioxidant therapy during serious intoxication vol.34, pp.1, 2011, https://doi.org/10.3109/01480545.2010.505238
  4. Glutathione‐dependent Bioactivation of Haloalkanes and Haloalkenes vol.36, pp.3-4, 2004, https://doi.org/10.1081/DMR-200033451
  5. Screening for reactive metabolites using electro-optical arrays featuring human liver cytosol and microsomal enzyme sources and DNA pp.36, 2009, https://doi.org/10.1039/b909372a
  6. Genotoxic Impurities in Pharmaceutical Manufacturing: Sources, Regulations, and Mitigation vol.115, pp.16, 2015, https://doi.org/10.1021/cr300095f
  7. Nature and nurture – lessons from chemical carcinogenesis vol.5, pp.2, 2005, https://doi.org/10.1038/nrc1546
  8. Determination of Hepatotoxicity and Its Underlying Metabolic Basis of 1,2-Dichloropropane in Male Syrian Hamsters and B6C3F1 Mice vol.145, pp.1, 2015, https://doi.org/10.1093/toxsci/kfv045
  9. Dose-response relationship, kinetics of formation, and persistence of S-[2-(N7-guanyl)-ethyl]glutathione-DNA adduct in livers of channel catfish (Ictalurus punctatus) exposed in vivo to ethylene dichloride vol.29, pp.7, 2010, https://doi.org/10.1002/etc.193
  10. Different sensitivity of BALB/c 3T3 cell clones in the response to carcinogens vol.25, pp.6, 2011, https://doi.org/10.1016/j.tiv.2011.05.032
  11. Contributions of Human Enzymes in Carcinogen Metabolism vol.25, pp.7, 2012, https://doi.org/10.1021/tx300132k
  12. Principles of covalent binding of reactive metabolites and examples of activation of bis-electrophiles by conjugation vol.433, pp.2, 2005, https://doi.org/10.1016/j.abb.2004.07.035
  13. Screening and characterization of variant Theta-class glutathione transferases catalyzing the activation of ethylene dibromide to a mutagen vol.47, pp.9, 2006, https://doi.org/10.1002/em.20252
  14. BALB/c 3T3 cell transformation assay for the prediction of carcinogenic potential of chemicals and environmental mixtures vol.24, pp.4, 2010, https://doi.org/10.1016/j.tiv.2010.03.003
  15. Assessment of the Genotoxicity of 1,2-Dichloropropane and Dichloromethane after Individual and Co-exposure by Inhalation in Mice vol.56, pp.3, 2014, https://doi.org/10.1539/joh.13-0236-OA
  16. Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters vol.40, pp.5, 2015, https://doi.org/10.2131/jts.40.647
  17. 7-Glutathione Pyrrole Adduct: A Potential DNA Reactive Metabolite of Pyrrolizidine Alkaloids vol.28, pp.4, 2015, https://doi.org/10.1021/tx500417q
  18. Thiols and the chemoprevention of cancer vol.7, pp.4, 2007, https://doi.org/10.1016/j.coph.2007.05.005
  19. Structural Basis of the Suppressed Catalytic Activity of Wild-type Human Glutathione Transferase T1-1 Compared to its W234R Mutant vol.355, pp.1, 2006, https://doi.org/10.1016/j.jmb.2005.10.049