Chromosomes Chromatid

CHROMATID One of the two components of each CHROMOSOME. Chromatids separate during cell division and each reproduces individually. 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

FIGURE 12.31 A model for chromosome structure, human chromosome 4. The 2-um DNA helix is wound twice around histone octamers to form 10-um uucleosomes, each of which contains 160 bp (80 per turn). These uucleosomes are then wound in solenoid fashion with six uucleosomes per turn to form a 30-nm filament. In this model, the 30-nm filament forms long DNA loops, each containing about 60,000 bp, which are attached at their base to the nuclear matrix. Eighteen of these loops are then wound radially around the circumference of a single turn to form a miniband unit of a chromosome. Approximately 10 of these minibands occur in each chromatid of human chromosome 4 at mitosis. 

Mitomycin C was found to have broad activity against a range of tumors and has been used clinically since the early 1960s [14, 15]. It causes many specific cellular effects, including inhibition of DNA synthesis, recombination, chromosome breakage, sister chromatid exchange, induction of DNA repair, and induction of... 

The eukaryotic somatic cell cycle is defined by a sequential order of tasks a dividing cell has to complete it must replicate its DNA, segregate its chromosomes, grow, and divide. The cell cycle can be divided into four discrete phases. DNA replication is restricted to S phase (DNA synthesis phase), which is preceded by a gap phase called G1 and followed by a gap phase called G2. During mitosis (M phase) the sister chromatids are segregated into two new daughter nuclei and mitosis is completed by the division of the cytoplasm termed cytokinesis (Fig. 1). 

The phase of the cell cycle where the sister chromatids are separated and distributed onto two daughter nuclei. First, upon entry into mitosis the chromosomes are condensed followed by the breakdown of the nuclear-envelope (prophase). The two centrosomes are separated and induce the formation of the mitotic spindle. Then, the chromosomes are captures by the spindle and aligned on the metaphase plate (metaphase). The sister-chromatids are separated and pulled to the poles of the spindle (anaphase). In telophase, two new nuclei are formed around the separated chromatids. 

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

Genotoxicity. No reliable data in humans exist to indicate whether methyl parathion may act by a genotoxic mechanism. One study reported a temporary but significant increase in chromatid breaks and stable chromosomal aberrations in two subjects after ingestion of methyl parathion (Van Bao et al. 1974), but another study reported no significant differences in five subjects after ingestion of methyl parathion when compared with 15 controls (Czeizel 1994). A study that involved combined inhalation and dermal exposure of workers to methyl parathion showed no increase in chromosomal aberrations in their... 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

Das P, John G. 1999. Induction of sister chromatid exchanges and chromosome aberrations in vivo in Etroplus suratensis (Bloch) following exposure to organophosphorus pesticides. Toxicol Lett 104 111-116. 

De Ferrari M, Artuso M, Bonassi S, et al. 1991. Cytogenic biomonitoring of an Italian population exposed to pesticides Chromosome aberration and sister-chromatid exchange analysis in peripheral blood lymphocytes. Mutat Res 260 105-113. 

Dulout FN, Pastori MC, Olivero OA, et al. 1985. Sister-chromatid exchanges and chromosomal aberrations in a population exposed to pesticides. Mutat Res 143 237-244. 

Gertain cells of insects, eg, Chironomus, contain giant chromosomes that have been repficated for ten cycles without separation of daughter chromatids. These copies of DNA fine up side by side in precise register and produce a banded chromosome containing regions of condensed chromatin and fighter bands of... 

At metaphase, mammalian chromosomes possess a twofold symmetry, with the identical duplicated sister chromatids connected at a centromere, the relative po-... 

The packaging of nucleoproteins within chromatids is not random, as evidenced by the characteristic patterns observed when chromosomes are stained with specific dyes such as quinacrine or Giemsa s stain (Figure 36-6). 

Figure 36-5. The two sister chromatids of human chromosome 12 (x 27,850). The location of the A+T-rich centromeric region connecting sister chromatids is indicated, as are two of the four telomeres residing at the very ends of the chromatids that are attached one to the other at the centromere. (Modified and reproduced, with permission, from DuPraw EJ DNA and Chromosomes. Holt, Rinehart, and Winston, 1970.)...

In diploid eukaryotic organisms such as humans, after cells progress through the S phase they contain a tetraploid content of DNA. This is in the form of sister chromatids of chromosome pairs. Each of these sister... 

Figure 36-12. Sister chromatid exchanges between human chromosomes. These are detectabie by Giemsa staining of the chromosomes of ceiis repiicated for two cycies in the presence of bromodeoxyuridine. The arrows indicate some regions of exchange. (Courtesy of S Wolff and J Bodycote.)...

Chromosomal aberrations Gene mutation Dominant lethal mutation Micronucleus formation Micronucleus formation Micronucleus formation Chromosomal aberrations Sister chromatid exchange Micronucleus formation Chromosomal aberrations Sister chromatid exchange DNA-protein cross-links Nondisjunction of Y chromosome in sperm DNA damage (single-strand breaks)... 

Splitting the chromosome cutting the ties that bind sister chromatids... 

Abstract. In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase. 

The chromatid separation process has also remained mysterious. It is an autonomous process that does not direcdy depend on the mitotic spindle (Wilson 1925, Mazia 1961). This is most vividly seen in cells whose spindles have been destroyed by spindle poisons such as colchicine. In many organisms, in particular in plant cells, the cell cycle delay induced by colchicine is only transient and chromatids eventually split apart in the complete absence of a mitotic spindle (Mole-Bajer 1958, Rieder Palazzo 1992) (Fig. 2). Mitosis in the presence of colchicine or colcemid (known as c-mitosis) leads to the production of daughter cells with twice the normal complement of chromosomes. This process is routinely used for manipulating plant genomes and may contribute to the therapeutic effects of taxol in treating breast cancer. 

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