Mechanisms involved in the induction of aneuploidy: the significance of chromosome loss

Abstract

The induction of aneuploidy by physical and chemical agents using different test systems was evaluated. The effect of X-rays, caffeine, acetaldehyde, ethanol, diethylstilbestrol, propionaldehyde, and chloral hydrate was studied by chromosome counting in Chinese hamster embryonic diploid cells. Aneugenic ability of cadmium chloride, cadmium sulfate, potassium dichromate, chromium chloride, nickel chloride, and nickel sulfate was assessed by means of anaphase-telophase analysis in Chinese hamster ovary cells. Chromosome counting in human fibroblasts (MRC-5 cell line) was employed to evaluate the effect of cacodilic acid, cadmium chloride, cadmium sulfate, and potassium dichromate. Finally, the induction of kinetochore-positive and kinetochore negative micronuclei by cadmium chloride, cadmium sulfate, potassium dichromate, chromium chloride, and nickel chloride was studied using CREST antibodies. When the effect of different agents was determined by chromosome counting, an increase of hypoploid but not of hyperploid cells was observed. Anaphase-telophase analysis showed that metal salts increased the frequency of lagging chromosomes. This finding has been confirmed by the increment of kinetochore-positive micronuclei using CREST antibodies. Therefore, chromosome loss could be considered as the main cause of induced aneuploidy.<br>A indução de aneuploidia por agentes físicos e químicos usando diferentes sistemas de teste foi avaliada. O efeito de raios-X, cafeína, acetaldeído, etanol, dietilestilbestrol, propionaldeído e hidrato de cloral foi estudado por contagem cromossômica em células diplóides embriônicas de hamster chinês. A habilidade aneugênica de cloreto de cádmio, sulfato de cádmio, dicromato de potássio, cloreto de crômio, cloreto de níquel e sulfato de níquel foi avaliada por meio de análise de anáfase-telófase em células de ovário de hamster chinês. A contagem cromossômica em fibroblastos humanos (linhagem celular MRC-5) foi empregada para avaliar o efeito de ácido cacodílico, cloreto de cádmio, sulfato de cádmio e dicromato de potássio. Finalmente, a indução de micronúcleos positivos e negativos para cinetocoro por cloreto de cádmio, sulfato de cádmio, dicromato de potássio, cloreto de crômio e cloreto de níquel foi estudada usando anticorpos CREST. Quando o efeito de agentes diferentes foi determinado por contagem cromossômica, observou-se um aumento de células hipoplóides mas não de hiperplóides. A análise anáfase-telófase mostrou que sais metálicos aumentaram a freqüência de cromossomos "lagging". Este achado foi confirmado pelo aumento de micronúcleos positivos para cinetocoro usando anticorpos CREST. Portanto, a perda cromossômica poderia ser considerada a principal causa de aneuploidia induzida

The Effect of Nickel and Zinc Addition to Rabbit Feed in Conjunction with the Risk of Chromosomal Aneuploidy

“…According to the results, we have found only hypodiploid cells from the group of aneuploid cells. A higher occurrence in the frequency of hypodiploid cells was also recorded by Seoane et al (2000) in their experiment focused on the evaluation of how Nickel salts affect Chinese hamster embryo cells (CHED) and human diploid fibroblasts (MRC-5) on the chromosomal level. An increase of hypoploid cell occurrence in our experiment was not the result of chromosome loss caused by technical factors; chromosomal number was counted only in metaphases surrounded by cytoplasm, as an indication of the integrity of the plasma membrane.…”

“…On the other hand, lagging chromosomes at mitosis produce 2 hypoploid daughter cells. Lagging chromatids originate a diploid and a hypoploid cell (Seoane et al 2000). The starters of this process are various internal and external factors including heavy metal exposure.…”

“…Aneuploidy presents a serious health problem and the reliability of any aneuploidy test is always challenged by the fact that the mechanisms involved in aneuploidy induction are poorly understood. Various test systems have been used to study chemical-induced aneuploidy (Seoane et al 2000). Only a few papers have described the aneuploidy-inducing property of nickel (Anderson 1985).…”

Evaluation of Cytotoxicity and Apoptotic Potential of Ophiorrhiza Pectinata Arn. – A Potent Anticancer Agent

“…The Mol and Thoppil same defect of the spindle fibers would be the reason for diagonal or disorientation of chromosomes and shift in MTOC [22]. Hyperploid cells would have emerged due to multipolar mitosis [23]. Pole-topole orientation of chromosomes at metaphase was also observed in cells, which would have resulted due to irregular pathways of spindle assembly and altered spindle activity [24].…”

Nuclear Polymorphism Induced Genomic Instability in Cluster Bean [<i>Cyamopsis tetragonoloba</i> (L.) Taub.] (Fabaceae)

“…MN designates genomic instability whereas its occurrence denotes a passage that genome tends to undergo nuclear restitution. The underlining repercussion of MN is aneuploidy (Seoane et al 2000). Microcell creation mediated enucleation may lead to paradigm shift in studying tumorigenic course and inheritance loss instilled through genetic ailments.…”