Aneuploidy

Genetic damage can take place at the level of the chromosome or at the gene level. In addition, chemicals can also induce alterations in the number of chromosomes in the cells. Aneuploidy is an excess or a shortage of a single chromosome. Polyploidia is an excess of a whole set of chromosomes tn the ceil. 

Assays for chromosome aberrations and micronuclei Assays for aneuploidy... 

The direct and indirect assessment of the aneuploidy-inducing potency of a number of organotin compounds was reported by Jensen et al. (1991a). The effects of dimethyltin dichloride, diphenyltin dichloride, trimethyltin chloride, tributyltin chloride, and triphenyl-tin chloride at 10 -10 mol/1 on chromosomal contractions in cultures of human peripheral lymphocytes were investigated. Diphenyltin dichloride, trimethyltin chloride, tributyltin chloride, and triphenyl-tin chloride appeared to be very strong inducers of chromosomal supercontraction, indicating that these compounds induce aneuploidy, probably by affecting... 

Jensen KG, Andersen O, Ronne M (1991a) Direct and indirect assessment of the aneuploidy-inducing potency of organotin compounds. Alternatives to Laboratory Animals, 19(2) 214-218. 

In a similar study, the lymphoeytes from live patients who ingested methyl parathion (Wofatox) in suicide attempts were examined for aneuploidy, chromatid aberrations, and ehromosome aberrations (Czeizel 1994). No significant differences from the 15 control patients were seen in these end points. 

Padungtod C, Hassold TJ, Millie E, et al. 1999. Sperm aneuploidy among Chinese pesticide factory workers Scoring by the FISH method. Am J Ind Med 36 230-238. 

On the other hand, chloral, a metabolite of trichloroethylene, which is also a mutagen and inducer of aneuploidy, is produced via a pathway which is more predominant in rats and humans than in mice (Kimbrough et al. 1985). A study using identical trichloroethylene concentrations in rats and mice, and which found increased aneuploidy in rats but no effect in mice, offered this mechanism as a possible explanation (Kligerman et al. 1994). An implication from this would be that humans are similarly more susceptible to chloral-mediated effects of trichloroethylene exposure. 

S. cerevisiae D61. M (loss of dominant color homolog) Mammalian cells Mitotic aneuploidy + + Koch et al. 1988... 

The pathologic evaluation of breast lesions serves to establish the histologic diagnosis and to confirm the presence or absence of other factors believed to influence prognosis. These prognostic factors include the presence of necrosis, lymphatic or vascular invasion, nuclear grade, hormone receptor status, proliferative index, amount of aneuploidy, and HER-2/neu expression. 

Fitzgerald PH, Pickering AF, Mercer JM, Miethke PM 1975 Premature centromere division a mechanism of non-disjunction causing X chromosome aneuploidy in somatic cells of man. Ann Hum Genet 38 417-428... 

Sargent, L.M. et al. (2009) Induction of aneuploidy by single-walled carbon nanotubes. Environmental and Molecular Mutagenesis, 50 (8), 708—717. 

Parry JM, Danford N, Parry EM. 1984. In vitro techniques for the detection of chemicals capable of inducing mitotic chromosome aneuploidy. Altern Lab Anim 11 117-128. 

Malekinejad H, Schoevers EJ, Daemen IJ, Zijlstra C, Colenbrander B, Fink-Gremmels F, Roelen BAJ (2007) Exposure of oocytes to the Fusarium toxins zearalenone and deoxynivalenol causes aneuploidy and abnormal embryo development in pigs. Biol Reprod 77 840-847 Maragos CM, Appell MD (2007) Capillary electrophoresis of the mycotoxin zearalenone using cyclodextrin-enhanced fluorescence. J Chromatogr A 1143 252-257... 

Aneuploidy in live births and abortions arises from aneuploid gametes during germ cell meiosis. Trisomy or monosomy of large chromosomes leads to early embryonic death. Trisomy of the smaller chromosomes allows survival but is detrimental to the health of an affected person, for example, Down s syndrome (trisomy 21), Patau syndrome (trisomy 13) and Edward s syndrome (trisomy 18). Sex chromosome trisomies (Klinefelter s and XXX syndromes) and the sex chromosome monosomy (XO), known as Turner s syndrome, are also compatible with survival. 

Aneuploidy in somatic cells is involved in the formation of human tumors. Up to ten percent of tumors are monosomic and trisomic for a specific chromosome as the single observable cytogenetic change. Most common among such tumors are trisomy 8, 9, 12, and 21 and monosomy for chromosomes 7, 22, and Y. 

Damage induced in whole animals can be detected in in vivo chromosome assays in either somatic or germinal cells by examination of metaphases or the formation of micronuclei. The micronucleus test can also detect whole chromosome loss or aneuploidy in the absence of clastogenic activity and is considered comparable in sensitivity to chromosome analysis (Tsuchimoto and Matter, 1979). 

Brook, J.D. and Chandley, A.C. (1985). Testing of 3 chemical compounds for aneuploidy induction in the female mouse. Mutation Res. 157 215-220. 

Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. A change in the number of chromosomes leads to a chromosomal disorder. These changes can occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. A gain or loss of chromosomes from the normal 46 is called aneuploidy. 

The most common form of aneuploidy is trisomy, or the presence of an extra chromosome in each cell. "Tri-" is Greek for "three" people with trisomy have three copies of a particular chromosome in each cell instead of the normal two copies. Down syndrome is an example of a condition caused by trisomy—people with Down syndrome typically have three copies of chromosome 21 in each cell, for a total of 47 chromosomes per cell. 

Aneuploidy The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol 2N-2), the loss of a single chromosome is monosomy (symbol 2N-1), the addition of a chromosome pair is tetrasomy (symbol 2N+2), the addition of a single chromosome is trisomy (symbol 2N+1). [nih]... 

Tsutsui T, Hayashi N, Maizumi H, et al. 1997. Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells. Mutat Res 373 113-123. 

Shekhar, M. P. V., Lyakhovigh, A., VisscHER, D. W., Heng, H., and Kondrat, N. Rad6 over-expression induces multinudeation, centrosom amplification, abnormal mitosis, aneuploidy, and transformation. 

Aneuploidy, which indicates a deviation from the euploid number of chromosomes, is the term used to describe the loss or gain of specific chromosomes. Two major types of aneuploidy are observed trisomy (three copies of a specific chromosome) and monosomy (one copy of a specific chromosome). Monosomies and trisomies are usually caused by nondisjunction (the failure of the two members of the chromosome pair to disjoin or separate) during meiosis (Fig II-3-2). All autosomal monosomies are lethal, but trisomies of three different autosomes (13,18, and 21) are compatible with survival to term in at least some cases. This difference illustrates the fact that the body tolerates extra genetic material more successfiiUy than a loss of genetic material. 

Aneuploidy affecting the sex chromosomes is relatively common and tends to have less severe consequences than does autosomal aneuploidy (although at least one X chromosome must be present for survival). Two aneuploidies of the sex chromosomes are clinically significant. 

Other common, but less clinically significant, sex chromosome aneuploidies are the 47,XXX (1/1,000 females) and 47,XYY (1/1,000 males) karyotypes. The former karyotype is associated with increased stature and a mild decrease in IQ, and the latter is associated with increased stature, mild decrease in IQ, acne, and a susceptibility to impulsive behavior (early studies suggesting a propensity to violent criminal behavior have not been substantiated). 

Aneuploidy (loss or gain of specific chromosomes, usually caused by nondisjunctior during meiosis) ... 

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