Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate

Toxicology Letters

Volumn 190, Issue 3, 2009, Pages 254-265

  Gocke, Elmar ^a   Bürgin, Heinrich ^a   Müller, Lutz ^a   Pfister, Thomas ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Alkylating agent; Dose response; Genotoxic impurity; Literature review; Risk assessment

Indexed keywords

BETA GALACTOSIDASE; ETHYLNITROSOUREA; MESYLIC ACID ETHYL ESTER; NELFINAVIR;

BLOOD TOXICITY; BONE MARROW TOXICITY; BRAIN TUMOR; BREAST TUMOR; CARCINOGENICITY; CHROMOSOME ABERRATION; CHROMOSOME DAMAGE; COMET ASSAY; CONCENTRATION (PARAMETERS); CYTOTOXICITY; DNA ADDUCT; DNA ALKYLATION; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; DRUG CONTAMINATION; EMBRYO DEVELOPMENT; EMBRYOTOXICITY; EXCISION REPAIR; FETOTOXICITY; FETUS DEVELOPMENT; FETUS MALFORMATION; GENE MUTATION; GENETIC DAMAGE; GENOTOXICITY; GERM CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; KIDNEY TUMOR; LETHAL DOSE; LIVER TUMOR; LUNG TUMOR; MEIOSIS; MICRONUCLEUS; MUTAGENICITY; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REFERENCE VALUE; REPRODUCTIVE TOXICITY; REVIEW; RISK ASSESSMENT; SOMATIC CELL; SPERMATOGONIUM; SPLEEN CELL; TERATOGENICITY; TOXICOKINETICS; TRANSGENE;

ABNORMALITIES, DRUG-INDUCED; ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; DNA; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG CONTAMINATION; ETHYL METHANESULFONATE; FEMALE; HIV PROTEASE INHIBITORS; HUMANS; MALE; MICE; NELFINAVIR; NEOPLASMS; NO-OBSERVED-ADVERSE-EFFECT LEVEL; RATS; REPRODUCTION; RISK ASSESSMENT; TOXICITY TESTS;

MUS;

EID: 70350181201     PISSN: 03784274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.toxlet.2009.03.016     Document Type: Review

References (79)

1. Alexander, P., Connell, D.I., 1963. The failure of the potent mutagenic chemical ethyl methane sulphonate to shorten the life-span of mice. In: Harris, R.J.C. (Ed.) Cellular Basis and Aetiology of Late Somatic Effects of Ionizing Radiation. A Symposium held in London March 27-30, 1962 Under Auspices of UNESCO and the IAEA, Academic Press, London, New York, pp. 259-265 (cited in: IARC monographs on the evaluation of carcinogenic risks to humans (1987)).
2. Anderson D., Hodge M.C.E., Palmer S., and Purchase I.F.H. Comparison of dominant lethal and heritable translocation methodologies. Mutat. Res. 85 (1981) 417-429
3. Arnold D.W., Kennedy G.L., Keplinger M.L., and Calandra J.C. Dominant lethal studies with alkylating agents: dose-response relationships. Toxicol. Appl. Pharmacol. 38 (1976) 79-84
4. Bateman J.R., Peters R.L., Mazen J.G., and Steingfeld J.I. Methly methanesulfonate (NSC-50256): phase I clinical study. Cancer Chemother. Rep. 50 (1966) 675-682
5. Beranek D.T. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat. Res. 231 (1990) 11-30
6. Bishop J.B., and Kodell R.L. The heritable translocation assay: its relationship to assessment of greater risk for future generation. Teratogen. Carcinog. Mutagen. 1 (1980) 305-322
7. Bruce W.R., and Heddle J.A. The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella, and sperm abnormality assays. Can. J. Genet. Cytol. 21 (1979) 319-334
8. Cammerer Z., Elhajouji A., and Suter W. In vivo micronucleus test with flow cytometry after acute and chronic exposures of rats to chemicals. Mutat. Res. 626 (2007) 26-33
9. Cattanach B.M., Pollard G.E., and Isaacson J.H. Ethyl methanesulfonate-induced chromosome breakage in the mouse. Mutat. Res. 6 (1968) 297-307
10. Clapp N.K. Carcinogenicity of nitrosamines and methanesulphonate esters given intraperitoneally in RF mice. Int. J. Cancer 12 (1973) 728-733
11. Clapp N.K., Craig A.W., and Toya R.E. Oncogenicity by methyl methanesulfonate in male RF mice. Science 161 (1968) 913-914
12. Cosentino L., and Heddle J.A. A comparison of the effects of diverse mutagens at the lacZ transgene and Dlb-1 locus in vivo. Mutagenesis 14 (1999) 113-119
13. Craddock V.M., and Frei J.V. Induction of tumours in intact and partially hepatectomized rats with ethyl methanesulphonate. Br. J. Cancer 34 (1976) 207-209
14. Doak S.H., Jenkins G.J., Johnson G.E., Quick E., Parry E.M., and Parry J.M. Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens. Cancer Res. 15 (2007) 3904-3911
15. Ehling U.H., and Neuhauser-Klaus A. Induction of specific-locus mutations in male mice by ethyl methanesulfonate (EMS). Mutat. Res. 227 (1989) 91-95
16. Fahrig R. The mammalian spot test (Fellfleckentest) with mice. Arch. Toxicol. 38 (1977) 87-98
17. Faustman E.M., Kirby Z., Gage D., and Varnum M. In vitro developmental toxicity of five direct-acting alkylating agents in rodent embryos: structure-activity patterns. Teratology 40 (1989) 199-210
18. Frei J.V. Tumour induction by low molecular weight alkylating agents. Chem. Biol. Interact. 3 (1971) 117-121 (cited in: IARC monographs on the evaluation of carcinogenic risks to humans (1987))
19. Frei V.J., Swenson H.D., Warren W., and Lawley P.D. Alkylation of deoxyribonucleic acid in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nirtosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma. Biochem. J. 174 (1978) 1031-1044
20. Generoso W.M., Bishop J.B., Goslee D.G., Newell G.W., Shen G.J., and von Halle E. Heritable translocation test in mice. Mutat. Res. 76 (1980) 191-215
21. Generoso W.M., Rutledge J.C., Cain K.T., Hughes L.A., and Downing D.J. Mutagen-induced fetal anomalies and death following treatment of females within hours after mating. Mutat. Res. 199 (1988) 175-181
22. Gerber, C., Toelle, H.-G., this issue. What happened: the chemistry side of the incident. Toxicol. Lett.
23. Gocke E., Wild D., Eckhardt K., and King M.T. Mutagenicity studies with the mouse spot test. Mutat. Res. 117 (1983) 201-212
24. Gocke, E., Ballantyne, M., Whitwell, J., Müller, L., this issue-a. Genotoxicity studies with ethyl methanesulfonate for micronuclei and lacZ gene mutation in mice. Toxicol. Lett.
25. Gocke, E., Wall, M., this issue b. In vivo genotoxicity of EMS: statistical assessment of the dose response curves. Toxicol. Lett.
26. Hartmann A., Schumacher M., Plappert-Helbig U., Lowe P., Suter W., and Müller L. Use of the alkaline in vivo Comet assay for mechanistic genotoxicity investigations. Mutagenesis 19 (2004) 51-59
27. Hashimoto T., Takeuchi K., Ohno S., Komatsu S., and Ohno Y. Cytogenic analysis of dominant lethal effects of mitomycin C and ethyl methanesulfonate. J. Toxicol. Sci. 12 (1987) 33-45
28. Heddle J.A., Hite M., Kirkhart B., Mavournin K., MacGregor J.T., Newell G.W., and Salamone M.F. The induction of micronuclei as a measure of genotoxicity. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat. Res. 23 (1983) 61-118
29. Hemsworth B.N. Embryopathies in the rat due to alkane sulphonates. J. Reprod. Fertil. 17 (1968) 325-334
30. Hrushesky W., Sampson D., and Murthey G.P. Carcinogenicity of ethylmethanesulphonate. J. Natl. Cancer Inst. 49 (1972) 1077-1083
31. Huttner E., Braun R., and Schoneich J. Mutagenic activity of isoniazid in the mouse. Pol. J. Pharmacol. Pharm. 31 (1979) 689-694 (see Russel et al., 1981)
32. IARC monographs on the evaluation of carcinogenic risks to humans, 1987. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs, vols. 1-42. Supplement 7.
33. Jackson H., Fox B.W., and Craig A.W. Antifertility substances and their assessment in the male rodent. J. Reprod. Fertil. 2 (1961) 447-465
34. 6-alkylguanine in hprt mutagenesis in T-lymphocytes of rats exposed in vivo to ethylmethanesulfonate, N-(2-hydroxyethyl)-N-nitrosourea, or N-ethyl-N-nitrosourea. Cancer Res. 55 (1995) 1875-1882
35. Katoh M., Cacheiro N.L., Cornett C.V., Cain K.T., Rutledge J.C., and Generoso W.M. Fetal anomalies produced subsequent to treatment of zygotes with ethylene oxide or ethyl methanesulfonate are not likely due to the usual genetic causes. Mutat. Res. 210 (1989) 337-344
36. Kondo K., Suzuki H., Hoshi K., and Yasui H. Micronucleus test with ethyl methanesulfonate administered by intraperitoneal injection and oral gavage. Mutat. Res. 223 (1989) 373-375
37. Kondo K., and Ozawa S. Micronucleus test with ethyl methanesulfonate in mouse peripheral blood reticulocytes stained supravitally using acridine orange-coated slides. Mutat. Res. 278 (1992) 109-111
38. Lang R. Mammalian spot test with moxnidazole, a 5-nitroimidazole. Experientia 34 (1978) 500-501
39. Lavé, T., Paehler, A., Grimm, H.P., Birnboeck, H., this issue. In vivo and in vitro characterization of ethyl methanesulfonate pharmacokinetics in animals and in human. Toxicol. Lett.
40. Lutz W.K. Dose-response relationship and low dose extrapolation in chemical carcinogenesis. Carcinogenesis 11 (1990) 1243-1247
41. Mientjes E.J., Luiten-Schuite A., van der Wolf E., Borsboom Y., Bergmans A., Berends F., Lohman P.H., Baan R.A., and van Delft J.H. DNA adducts, mutant frequencies, and mutation spectra in various organs of lambda lacZ mice exposed to ethylating agents. Environ. Mol. Mutagen. 31 1 (1998) 18-31
42. Montesano R., Mohr U., Magee P.N., Hilfrich J., and Haas H. Additive effect in the induction of kidney tumours in rats treated with dimethylnitrosamine and ethylmethanesulphonate. Br. J. Cancer 29 (1974) 50-58
43. Müller, L., Singer, T., this issue. Chronological overview of events and testing strategy. Toxicol. Lett.
44. Müller, L., Gocke, E., Lavé, T., Pfister, T., this issue. Ethyl methanesulfonate toxicity in Viracept-a comprehensive human risk assessment based on threshold data for genotoxicity. Toxicol. Lett.
45. Murphy G.P., Mirand E.A., Johnson G.S., Schmidt J.D., and Scott W.W. Renal tumors induced by a single dose of dimethylnitrosamine: morphologic, functional, enzymatic, and hormonal characterizations. Invest. Urol. 4 (1966) 39-56
46. NTP studies on EMS: see http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.sea rchresults&searchterm=62-50-0.
47. Op het Veld C.W., van Hees-Stuivenberg S., van Zeeland A.A., and Jansen J.G. Effect of nucleotide excision repair on hprt gene mutations in rodent cells exposed to DNA ethylating agents. Mutagenesis 12 (1997) 417-424
48. Partington M., and Jackson H. Induction of dominant lethal mutations in rat by alkane sulfonic esters. Genet. Res. 4 (1963) 333-345
49. Piegorsch W.W., Lockhart A.C., Carr G.J., Margolin B.H., Brooks T., Douglas G.R., Liegibel U.M., Suzuki T., Thybaud V., van Delft J.H., and Gorelick N.J. Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: an interlaboratory study. Mutat. Res. 388 (1997) 249-289
50. Platzek T., Bochert G., Schneider W., and Neubert D. 1. Ethylmethanesulfonate as a teratogen in mice. Arch. Toxicol. 51 (1982) 1-25
51. Platzek T., Bochert G., Rahm U., and Neubert D. Embryotoxicity induced by alkylating agents. Some methodological aspects of DNA alkylation studies in murine embryos using ethylmethanesulfonate. Z. Naturforsch. [C] 42 (1987) 613-626
52. Platzek T., Borchert G., and Rahm U. Embryotoxicity induced by alkylating agents. 8. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos. Teratogen. Carcinogen. Mutagen. 14 (1994) 65-73
53. Platzek T., Bochert G., and Meister R. Embryotoxicity induced by alkylating agents. 9. Low dose prenatal-toxic risk on no-observed-adverse-effect-level risk factor approach, dose-response relationships, and molecular dosimetry. Teratogen. Carcinogen. Mutagen. 15 (1995) 81-92
54. Robbiano L., Parodi A., Venturelli S., and Brambilla G. Comparison of DNA alkylation, fragmentation, and repair in maternal and fetal tissues of pregnant rats treated with a single dose of ethyl methanesulfonate, ethyl-n-nitrosourea, n- nitrosodiethylamine, and methyl-n-nitrosourea. Teratogen. Carcinogen. Mutagen. 9 (1989) 157-166
55. Roe F.J.C., Walters M., and Mitchley B.C.V. Carcinogenesis tests using newborn mice. A. R. Br. Emp. Cancer Campgn. 40 (1962) 42-43 (cited in: IARC monographs on the evaluation of carcinogenic risks to humans, 1987)
56. Roe F.J.C., Mitchley B.C.V., and Walters M. Tests for carcinogenesis using newborn mice: 1,2-benzanthracene, 2-naphthylamine, 2-naphthyl-hydroxylamine and ethyl methane sulfonate. Br. J. Cancer 17 (1963) 255-260
57. Russell L.B., Selby P.B., von Halle E., Sheridan W., and Valcovic L. Use of the mouse spot test in chemical mutagenesis: interpretation of past data and recommendations for future work. Mutat. Res. 86 (1981) 355-379
58. Schneider J., Warzok R., Schreiber D., and Heiderstädt R. Postnatal and transplacental carcinogenic effects of methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) in hooded rats. Exp. Pathol. 16 (1978) 157-167
59. Sega G.A. A review of the genetic effects of ethyl methanesulfonate. Mutat. Res. 134 (1984) 113-142
60. Segal A., and Sellakumar A. Inducibility of thymic lymphomas in female Hsd: (ICR)BR mice following subcutaneous injection of ethy- and isopropylmethansulfonate. Cancer Lett. 44 (1989) 199-204
61. Smith C.C., Adkins D.J., Martin E.A., and O'Donovan M.R. Recommendations for design of the rat Comet assay. Mutagenesis 23 (2008) 233-240
62. Soares E.R., and Crenshaw J.W. Dominant lethal mutations induced in mice by orally administered ethyl methanesulfonate. Mutat. Res. 26 (1974) 385-389
63. Soares E.R. Studies of factors influencing the mutagenicity of EMS in mice. Mutat. Res. 37 (1976) 245-252
64. Stumpf R., Margison G.P., Montesano R., and Pegg A.E. Formation and loss of alkylated purines from DNA of hamster liver after administration of dimethylnitrosamine. Cancer Res. 39 (1979) 50-54
65. Suzuki T., Hayashi M., Wang X., Yamamoto K., Ono T., Myhr B.C., and Sofuni T. A comparison of the genotoxicity of ethylnitrosourea and ethyl methanesulfonate in lacZ transgenic mice (Muta Mouse). Mutat. Res. 395 (1997) 75-82
66. Swann P.F., and Magee P.N. Induction of rat kidney tumours by ethyl methanesulphonate and nervous tissue tumours by methyl methanesulphonate and ethyl methanesulphonate. Nature 223 (1969) 947-949
67. Teaf C.M., Harbison R.D., and Bishop J.B. Germ-cell mutagenesis and GSH depression in reproductive tissue of the F-344 rat induced by ethyl methanesulfonate. Mutat. Res. 144 (1985) 93-98
68. Teaf C.M., Bishop J.B., and Harbison R.D. Potentiation of ethyl methanesulfonate-induced germ cell mutagenesis and depression of glutathione in male reproductive tissues by 1,2-dibromoethane. Teratogen. Carcinogen. Mutagen. 10 (1990) 427-438
69. Teramoto S., Saito R., Asyama H., and Shirasu Y. Dominant lethal mutations induced in male rats by 1,2-dibromo-3-chloropropane (DBCP). Mutat. Res. 77 (1980) 71-78
70. Trzos R.J., Petzold G.L., Brunden M.N., and Swenberg J.A. The evaluation of sixteen carcinogens in the rat using the micronucleus test. Mutat. Res. 58 (1978) 79-86
71. Tudor R.J., Severs N.J., and Hicks R.M. The induction of urothelial hyperplasia by methyl methanesulphonate and ethyl methanesulphonate. Br. J. Cancer 48 (1983) 289-300
72. Ueo H., Takaki R., Yamagami H., Nakano S., Okeda T., and Sakakibira K. High incidence of rat mammary carcinoma by oral administration of ethyl methanesulfonate. Cancer Lett. 7 (1979) 79-84
73. Ueo H., Takaki R., Yamagami H., and Sugimachi K. Mammary carcinoma induced by oral administration of ethyl methanesulphonate. Determination of some of the parameters affecting tumor induction. Carcinogenesis 2 (1981) 1223-1228
74. Ueo H., Matsuoka H., Akiyoshi T., Sugimachi K., and Takaki R. Estrogen receptor status and effects od endocrine ablative surgery in ethyl methanesulphonate-induced rat mammary carcinoma. Cancer Lett. 51 (1990) 151-155
75. Ueo H., Matsuoka H., Honda M., Inoue H., Takaki R., and Akiyoshi T. Chemopreventive effects of tamoxifen in ethyl methanesulfonate-induced rat mammary carcinogenesis. Cancer Lett. 71 (1993) 19-24
76. van Delft J.H., Bergmans A., van Dam F.J., Tates A.D., Howard L., Winton D.J., and Baan R.A. Gene-mutation assays in lambda lacZ transgenic mice: comparison of lacZ with endogenous genes in splenocytes and small intestinal epithelium. Mutat. Res. 415 (1998) 85-96
77. Walters M.A., Roe F.J.C., Mitchley B.C.V., and Walsh A. Further tests for carcinogenesis using newborn mice: 2-naphthylamine, 2-naphthylhydroxamine, 2-acetylaminofluorene and ethyl methane sulfonate. Br. J. Cancer 21 (1967) 367-372
78. Williams P.D., Hrushesky W., Gaeta J.F., and Murphy G.P. Influence of hormone therapy on rats treated with the carcinogen EMS. Res. Commun. Chem. Pathol. Pharmacol. 7 (1974) 25-30
79. Witt K.L., Livanos E., Kissling G.E., Torous D.K., Caspary W., Tice R.R., and Recio L. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat. Res. 649 (2007) 101-113