Summary
Diethylstilbestrol (DES) and estradiol (E2) are know inducers of micronuclei (MN) in several cell systems. DES is able to interfere with the spindle apparatus of mitotic cells. This mechanism is discussed to be the cause of chromosomal nondisjunction and subsequently of MN formation. We have tested several steroidal and stilbene estrogens for their ability to induce MN in cultured primary fibroblasts from Syrian hamster embryos and sheep seminal vesicles. All compounds tested, i.e., E2, 2-hydroxy-E2, 4-hydroxy-E2, DES, 3,4-bis-(m-hydroxyphenyl)-hex-3-ene, indenestrol A and indenestrol B gave rise to MN in both cell systems. To further elucidate the mechanism of MN induction, we have scored the MN for the presence of chromatids by CREST antikinetochore immunofluorescence staining. In both cell systems, the frequency of kinetochore-positive MN increased significantly but not uniformly for all estrogens. We conclude that the compounds tested in this study induce MN not exclusively via disturbances of the mitotic spindle apparatus. A second mechanism, possibly an interaction with the kinetochore structure could be responsible for the induction of kinetochore-negative MN.
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References
Tsutsui T, Maizumi H, McLachlan JA, Barrett JC (1983) Aneuploidy induction and cell transformation by diethylstilbestrol: a possible chromosomal mechanism in carcinogenesis, Cancer Res 43: 3814–3821.
Tsutsui T, Suzuki N, Fukuda S, Sato M, Maizumi H, McLachlan JA, Barrett JC (1987) 17ß-Estradiol-induced cell transformation and aneuploidy of Syrian hamster embryo cells in culture. Carcinogenesis 8: 1715–1719.
Schmuck G, Lieb G, Wild D, Schiffmann D, Henschler D (1988) Characterization of an in vitro micronucleus assay with Syrian hamster embryo fibroblasts. Mut Res 203: 397–404.
Wheeler WJ, Cherry LM, Downs T, Hsu TC (1986) Mitotic inhibition and aneuploidy induction by naturally occurring and synthetic estrogens in Chinese hamster cells in vitro. Mut Res 171: 31–41.
Tucker RW, Barrett JC (1986) Decreased number of spindle and cytoplasmic microtubules in hamster embryo cells treated with a carcinogen, diethylstilbestrol. Cancer Res 46: 2088–2095.
Wheeler WJ, Hsu TC, Tousson A, Brinkley BR (1987) Mitotic inhibition and chromosome displacement induced by estradiol in Chinese hamster cells. Cell Motil and Cytoskel 7: 235–247.
Epe B, Hegler J, Metzler M (1987) Site-specific covalent binding of stilbene-type and steroidal estrogens to tubulin following metabolic activation in vitro. Carcinogenesis 8: 1271–1275.
Tucker JD, Eastmond DA (1990) Use of an antikinetochore antibody to discriminate between micronuclei induced by aneuploidogens and clastogens. Mutat Environ, Part B: 275–284.
Epe B, Schiffmann D, Metzler M (1986) Possible role of oxygen radicals in cell transformation by diethylstilbestrol and related compounds. Carcinogenesis 7: 1329–1334.
Liehr JG, Roy D (1990) Free radical generation by redox cycling of estrogens. Free Radical Biol Med 8: 415–423.
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© 1992 Springer-Verlag New York, Inc.
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Schnitzler, R., Metzler, M. (1992). Properties of Micronuclei Induced by Various Estrogens in Two Different Mammalian Cell Systems. In: Li, J.J., Nandi, S., Li, S.A. (eds) Hormonal Carcinogenesis. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-9208-8_49
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DOI: https://doi.org/10.1007/978-1-4613-9208-8_49
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