The detection, definition and regulation of aneugenic chemicals

Parry, James M.; Parry, Elizabeth M.; Ellard, Sian; Warr, T.; O’Donovan, Joye; Lafi, Anna

doi:10.1007/978-3-642-84938-1_31

Cited by 9 publications

(1 citation statement)

References 36 publications

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“…The maintenance of the stability of the genome is dependent upon the coordinated functioning of the cell division cycles (Parry et al, 1993). Deviations from the normal functioning of the cell division process may occur spontaneously or result from exposure to environmental agents; these may lead to chromosomal malsegregation and the production of cells with abnormal chromosome numbers.…”

Section: Introductionmentioning

confidence: 99%

Cell cycle dependent aneuploidy induction by x-rays in vitro in human lymphocytes

Tallon¹,

Verschaeve²,

Kirsch‐Volders³

1998

Microsc. Res. Tech.

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Section: Introductionmentioning

confidence: 99%

Cell cycle dependent aneuploidy induction by x-rays in vitro in human lymphocytes

Tallon¹,

Verschaeve²,

Kirsch‐Volders³

1998

Microsc. Res. Tech.

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Aneuploidy in germ cells: Disruption of chromosome mover components

1996

Environ. Mol. Mutagen.

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Indications for a threshold of chemically‐induced aneuploidy in vitro in human lymphocytes

Elhajouji

Kirsch‐Volders

1995

Environ and Mol Mutagen

163

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The possible existence of a threshold for compounds inducing chromosomal loss was investigated for four known aneugens (colchicine, COL; carbendazim, MBC; mebendazole, MEB; nocodazole, NOC) and two clastogens (methyl methanesulfonate, MMS; mitomycin C, MMC) using the micronucleus (MN) test in human lymphocytes. The presence of a whole chromosome in the MN was studied by fluorescent in situ hybridization (FISH) using a synthetic pancentromeric oligonucleotide probe. FISH was applied on two different MN preparations: cytokinesis-blocked MN (MNCB) assay, and MN sorted by flow cytometry. At subtoxic concentrations analyzed by MNCB and FISH, COL, MEB, MBC, and NOC induced a concentration-dependent increase in centromere-positive MN (MNCen+). MMC seemed to induce an increase in both types of MN (MNCen- and MNCen+), while MMS induced only MNCen-. On the sorted micronuclei (in a wide range of low to subtoxic concentrations), the concentration-effect profile for MNCen+, with the four aneugens tested, showed a statistically nonsignificant increase over a range of concentrations, followed by a second range of high concentrations with a statistically significant increase. To analyze the existence of a threshold, a piecewise linear regression was applied to the data. The first concentration that showed a statistically significant increase in MNCen+ was chosen as a breakpoint (0.037 microM for COL, 2.62 microM for MBC, 0.27 microM for MEB, and 0.066 microM for NOC). The statistical correlation between observed and predicted values showed a high correlation (r = 0.99), indicating a clear threshold for aneuploidy induction. However, for MMS the concentration-effect profile for MNCen+ showed a continuous concentration-dependent decrease with no threshold. With the two cytotoxicity assays used (Bio-Rad and MTT), no significant reduction was detected either in the protein content or in mitochondrial succinate dehydrogenase activity with all chemicals tested for MN induction. Therefore, our data suggest that the observed thresholds were not due to indirect toxic effects but to real aneugenic effects.

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The detection, definition and regulation of aneugenic chemicals

Cited by 9 publications

References 36 publications

Cell cycle dependent aneuploidy induction by x-rays in vitro in human lymphocytes

Cell cycle dependent aneuploidy induction by x-rays in vitro in human lymphocytes

Aneuploidy in germ cells: Disruption of chromosome mover components

Indications for a threshold of chemically‐induced aneuploidy in vitro in human lymphocytes

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