Carcinogenic and possible mutagenic effects of stilboestrol in offspring exposed in utero

Bishun, N. P.; Smith, Neil; Williams, Donald C.; Raven, Ronald W.

doi:10.1002/jso.2930090312

Cited by 9 publications

(1 citation statement)

References 25 publications

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“…Whole chromosome loss during the anaphase transition induced number of metaphases displaying undercondensation of a particular chromosome has to be reach a certain level before by DES fits well with the observation that this drug does not induce structural chromosome aberrations (Abe and Sasaki, its increased occurrence becomes apparent in corresponding MN. A similar correlation has been noted in lymphocytes 1977; Bishun et al, 1977;Ishidate and Odashima, 1977;Dean, 1981; this investigation). treated with 5-azacytidine (Guttenbach and Schmid, 1994;Fauth et al, 1998) and idoxuridine (Tommerup, 1984;Fauth Frequency of human chromosome material in DES-induced and Zankl, 1999).…”

Section: Des Induces Elevated Mn Frequencies and Numerical Chromosomesupporting

confidence: 65%

Chromosome painting reveals specific patterns of chromosome occurrence in mitomycin C- and diethylstilboestrol-induced micronuclei

2000

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Tucker, 1989) or by FISH with pan-centromeric DNA probes D-67653 Kaiserslautern, Germany (Becker et al., 1990, Miller et al., 1992. The drugs that have Cultures of human blood lymphocytes from three subjects been studied in most detail for their mechanism of MN were incubated with the clastogen mitomycin C (MMC, induction are the clastogen mitomycin C (MMC) (e.g. Miller 500 ng/ml) and the aneugen diethylstilboestrol (DES, and Adler, 1990;Miller et al., 1991; Rudd et al., 1991; 80 µM) 23 h before harvesting, to induce formation of Surrallés et al., 1995) and the aneugen diethylstilboestrol micronuclei (MN) and numerical and structural alterations (DES) (e.g. Eastmond and Tucker, 1989;Migliore et al., 1996). in metaphase chromosomes. We used fluorescence in situ Many studies have addressed the mechanisms of MN induchybridization (FISH) with painting probes for all human tion (see above), but only a few investigators have examined chromosomes to determine which chromosomes had conthe chromosomal content of MN. The latter studies have shown tributed material to the induced MN. MMC treatment that some mutagens induce preferential occurrence of particular induced an~18-fold increase in MN and led to a significant chromosomes in MN. Chromosomes 1, 9, 15, 16 and Y were increase in hypodiploidy and structural chromosome found in elevated frequencies in 5-azacytidine-induced MN aberrations in metaphase preparations. Undercondensation (Guttenbach and Schmid, 1994; Fauth et al., 1998), chromoof pericentromeric heterochromatin of chromosomes 9 and some 9 in idoxuridine-induced MN (Tommerup, 1984; 1 occurred in 20-75% of metaphases and FISH disclosed Fauth and Zankl, 1999), chromosome 7 in colcemid-induced an abundance of material from these chromosomes in MN (Wuttke et al., 1997) and acrocentric chromosomes in induced MN (62-69% from chromosome 9 and 7-12% from vanadium-and colcemid-induced MN (Migliore et al., 1995; chromosome 1). DES treatment of lymphocytes induced a Caria et al., 1996). seven-fold increase in MN frequency and four-fold increaseUsing FISH analysis with whole chromosome painting in the frequency of numerical aberrations; structural probes (WCPs) for all human chromosomes (Fauth et al., aberrations were not significantly increased. FISH analysis 1998), we investigated which chromosomes had contributed showed that material from all chromosomes was present material to induced MN in MMC-and DES-treated short-term in DES-induced MN, with material from chromosome 1 human lymphocyte cultures. WCPs target the euchromatic present in 16% of MN and material from each other parts of a chromosome and thereby disclose both whole chromosomes being present in 2-10% of MN. Material chromosomes and acentric fragments in MN. However, they from chromosomes 14, 19 and 21 was significantly more fail to distinguish between an entire chromosome or material frequent material from chromosome Y significantly less from a large chromosomal fragment(s) in a particular MN. frequent in DES-treated cells than in controls. The findings...

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Section: Des Induces Elevated Mn Frequencies and Numerical Chromosomesupporting

confidence: 65%

Chromosome painting reveals specific patterns of chromosome occurrence in mitomycin C- and diethylstilboestrol-induced micronuclei

2000

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Dose-response studies of the induction of hyperdiploidy and polyploidy by diethylstilbestrol and 17β-estradiol in cultured human lymphocytes using multicolor fluorescence in situ hybridization

Schuler

Hasegawa

Parks

et al. 1998

Environ. Mol. Mutagen.

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Diethylstilbestrol (DES) and 17β‐estradiol (E2) are known inducers of aneuploidy and polyploidy in vivo and in vitro. Isolated human lymphocytes were treated with the stilbene estrogen DES (0.05–50 μM) and the steroid estrogen E2 (0.05–75 μM) in culture. Multicolor fluorescence in situ hybridization (FISH) with DNA probes for the centromere and adjacent heterochromatin regions of chromosomes 1, 9, and 16 was used to detect hyperdiploidy, polyploidy, and chromosomal breakage affecting these chromosomes. Using this FISH technique, significant nonlinear increases in hyperdiploidy were observed with both compounds, whereas no induction of chromosomal breakage affecting the pericentric heterochromatin regions of chromosomes 1, 9, and 16 could be detected. DES induced a maximum of approximately 13% hyperdiploid cells at 30 μM, whereas E2 showed its highest induction at 75 μM with 7% hyperdiploid cells. To distinguish hyperdiploidy from polyploidy, a FISH labeling strategy to detect multiple chromosomes simultaneously was established. Using this approach, we could show that most of the cells showing multiple hybridization regions after treatment with both chemicals were most likely the result of polyploidy rather than true hyperdiploidy. These results indicate that the induction of hyperdiploidy/polyploidy with DES and E2 show sublinear dose‐response relationships with likely threshold concentrations in human lymphocytes and that FISH with multiple probes targeting different chromosomes can be used to estimate hyperdiploidy and polyploidy frequencies. Environ. Mol. Mutagen. 31:263–273, 1998 © 1998 Wiley‐Liss, Inc.

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The Kinetochore of Mammalian Chromosomes: Structure and Function in Normal Mitosis and Aneuploidy

1985

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Carcinogenic and possible mutagenic effects of stilboestrol in offspring exposed in utero

Cited by 9 publications

References 25 publications

Chromosome painting reveals specific patterns of chromosome occurrence in mitomycin C- and diethylstilboestrol-induced micronuclei

Chromosome painting reveals specific patterns of chromosome occurrence in mitomycin C- and diethylstilboestrol-induced micronuclei

Dose-response studies of the induction of hyperdiploidy and polyploidy by diethylstilbestrol and 17β-estradiol in cultured human lymphocytes using multicolor fluorescence in situ hybridization

The Kinetochore of Mammalian Chromosomes: Structure and Function in Normal Mitosis and Aneuploidy

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