Induction of micronuclei by mitomycin C and colchicine in the marine mussel Mytilus galloprovincialis

Majone, Franca; Brunetti, Riccardo; Fumagalli, O.; Gabriele, M.; Levis, Angelo Gino

doi:10.1016/0165-7992(90)90064-q

Cited by 27 publications

(21 citation statements)

References 9 publications

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“…This possibility was inferred from the fact that micronucleus frequencies induced by a clastogenic agent (mitomycin C) persist for a very long time after the end of treatment (Majone et al 1987). We later also showed that an aneuploidizing substance (colchicine) has the same effect (Majone et al 1990), confirming the validity of the test in environmental studies.…”

Section: Introductionsupporting

confidence: 60%

The micronucleus test: temporal pattern of baseline frequency in Mytilus galloprovincialis

Brunetti¹,

Gabriele²,

Valerio³

et al. 1992

Mar. Ecol. Prog. Ser.

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Section: Introductionsupporting

confidence: 60%

The micronucleus test: temporal pattern of baseline frequency in Mytilus galloprovincialis

Brunetti¹,

Gabriele²,

Valerio³

et al. 1992

Mar. Ecol. Prog. Ser.

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“…We evaluated FB 1 genotoxic potential with an in vitro micronucleus assay, which is one of the preferred methods for assessing chromosome damage. For our positive controls we used colchicine, a spindle-damaging agent, as a model aneugen, and mitomycin C, an agent directly damaging the chromosomes, as a model clastrogen (Majone et al 1990;Vanparys et al 1990;Caria et al 1996;Liu et al 1998;Nishikawa et al 1999;Nesti et al 2000). In each sample, binucleate cells with well-preserved nuclei and cytoplasm were analysed and micronuclei were counted under a light microscope at ·1000 magnification.…”

Section: Fumonisin B 1 Is Genotoxic To Rk13 Cellsmentioning

confidence: 99%

Cytotoxic and genotoxic effects of fumonisin B1 on rabbit kidney RK13 cell line

et al. 2002

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Fumonisins, mycotoxins produced by certain strains of Fusarium moniliforme, could induce various diseases in animals and are suspected human carcinogens. Fumonisin B1 (FB1), the most commonly found fumonisin, has been characterised as a tumour initiator and a tumour promoter, a mitogen and an anti-proliferative agent. In this study we examined the cytotoxicity and genotoxicity of FB1 in rabbit kidney RK13 cells. To evaluate the effects of FB1 on survival of this cell line we analysed cell viability, membrane integrity, DNA fragmentation and overall morphology of the cells. The genotoxic potential of FB1 was estimated by monitoring the ability of this mycotoxin to induce micronuclei in RK13 cells. Exposure to FB1 caused a significant increase in micronucleus frequency in a concentration- and in a time-dependent manner. Nanomolar concentrations of FB1 decreased cell viability after 24 h and even more so after 48 h of exposure. The morphological changes observed suggested that an increased number of RK13 cells were dying by the process of apoptosis. However, FB1 also induced impairments of cell and mitochondrial membrane integrity, as assessed by lactate dehydrogenase and glutamate dehydrogenase leakage. These results could imply that nanomolar concentrations of FB1 induced apoptosis, which subsequently may proceed to secondary necrosis. In summary, our observations suggest that FB1 is genotoxic and cytotoxic to RK13 cells.

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“…The cells were collected 48 h later by trypsinization and were washed in phosphate-buffered saline and fixed in Carnoy's fixative (methanol/acetic acid 3:1, v/v) for 15 min. Interphase preparations were obtained following the procedures described previously (7,8).…”

Section: Methodsmentioning

confidence: 99%

“…MN are small nuclei-like bodies found outside the main nucleus produced as consequences of chromosomal damage (7,8). They exist at a low prevalence in cells ambiently and can be induced ex vivo by genotoxic compounds with different mechanisms of action.…”

mentioning

confidence: 99%

Clastogenic Effect of the Human T-cell Leukemia Virus Type I Tax Oncoprotein Correlates with Unstabilized DNA Breaks

Majone¹,

Jeang²

2000

Journal of Biological Chemistry

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Expression of the human T-cell leukemia virus type I (HTLV-I) Tax oncoprotein rapidly engenders DNA damage as reflected in a significant increase of micronuclei (MN) in cells. To understand better this phenomenon, we have investigated the DNA content of MN induced by Tax. Using an approach that we termed FISHI, fluorescent in situ hybridization and incorporation, we attempted to characterize MN with centric or acentric DNA fragments for the presence or absence of free 3-OH ends. Free 3-OH ends were defined as those ends accessible to in situ addition of digoxigenin-dUTP using terminal deoxynucleotidyl transferase. MN were also assessed for centromeric sequences using standard fluorescent in situ hybridization (FISH). Combining these results, we determined that Tax oncoprotein increased the frequency of MN containing centric DNA with free 3-OH and decreased the frequency of MN containing DNA fragments that had incorporation-inaccessible 3-ends. Recently, it has been suggested that intracellular DNA breaks without detectable 3-OH ends are stabilized by the protective addition of telomeric caps, while breaks with freely detectable 3-OH are uncapped and are labile to degradation, incomplete replication, and loss during cell division. Accordingly, based on increased detection of free 3-OH-containing DNA fragments, we concluded that HTLV-I Tax interferes with protective cellular mechanism(s) used normally for stabilizing DNA breaks.

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Induction of micronuclei by mitomycin C and colchicine in the marine mussel Mytilus galloprovincialis

Cited by 27 publications

References 9 publications

The micronucleus test: temporal pattern of baseline frequency in Mytilus galloprovincialis

The micronucleus test: temporal pattern of baseline frequency in Mytilus galloprovincialis

Cytotoxic and genotoxic effects of fumonisin B1 on rabbit kidney RK13 cell line

Clastogenic Effect of the Human T-cell Leukemia Virus Type I Tax Oncoprotein Correlates with Unstabilized DNA Breaks

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