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

Abstract

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...

Genotoxic and Anti-Genotoxic Effects of Vanillic Acid Against Mitomycin C-Induced Genomic Damage in Human Lymphocytes In Vitro

“…In our study, MMC generated a high MN and a low NDI in the CBMN assay and a high GDI and an increased percentage of damaged cells in the alkaline comet assay. These findings agree with other studies that showed mutagenic and clastogenic activity for MMC (Fauth et al, 2000;Krishnaja and Sharma, 2008;Sontakke and Fulzele, 2009). It has been reported that in vivo vanillin treatment decreased the MMC-induced MN ratio in the bone marrow of mice (Inouye et al, 1988).…”

“…MMC is a highly genotoxic agent that induces chromosomal aberrations and sister chromatid exchanges in cultured human blood lymphocytes (Krishnaja and Sharma, 2008), increases MN frequency (Fauth et al, 2000) and induces higher MN formation in human liver fibroblast cultures (Nesti et al, 2000). In our study, MMC generated a high MN and a low NDI in the CBMN assay and a high GDI and an increased percentage of damaged cells in the alkaline comet assay.…”

Cytogenetic, cytotoxic and GC–MS studies on concrete and absolute oils from Taif rose, Saudi Arabia

“…In this study, we used this antitumor-antibiotic drug to test the possible antimutagenic activity of concrete and absolute oils. The study results of MMC in this experiment were coincided with previous reports (Fauth et al 2000;Yogesh and Fulzele 2009;Unal et al 2013). The group treated with MMC alone showed a significant elevation of chromosomal damage.…”

“…This would inhibit DNA replication and probably might be the antitumor action of this drug. Despite the fact that MMC showed antitumor action, many reports proved that it may cause high frequency of chromosomal aberrations, sister chromatid exchanges and micronuclei formation (Latt 1974;Fauth et al 2000;Yogesh and Fulzele 2009). In this study, we used this antitumor-antibiotic drug to test the possible antimutagenic activity of concrete and absolute oils.…”

Chromosomal Composition of Micronuclei in Human Leukocytes Exposed to Mitomycin C

“…However, gene density and chromosome position in nuclei have a tendency of slightly influencing MMC-induced MN formation. The explanation for this tendency can be the exceptional high contribution in MN formation of chromosome 9 with low gene density and peripheral location in nuclei, caused by its high sensitivity to ММС (Fauth et al 2000). However, further studies are certainly needed to clarify the mechanisms of MN formation.…”