Chromatid binding

Swiss mouse (liver chromatin) Chromatid binding + Bryan et al. 1974... 

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. 

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

Loss of sister chromatid cohesion would therefore be sufficient for the sudden movement of chromatids to opposite poles at the metaphase to anaphase transition. According to this hypothesis, a specific apparatus binds chromatids together during replication, holds them in an orientation that facilitates the attachment of sister kinetochores to spindles extending to opposite poles, and resists the splitting force that results from this bipolar attachment to the spindle. Destruction of this specialized cohesive structure triggers movement of chromatids to opposite poles at the onset of anaphase. 

Nitro PAHs have been shown to exhibit a large variety of biological activities. Included in these are the induction of mutations in bacterial (Table I) and eukaryotic cells (9,17,54-57), the neoplastic transformation of cultured mammalian cells (58-59), and the induction of DNA strand breaks (60), DNA repair (61-62), sister chromatid exchanges (63-64), and chromosomal aberrations (65-66). Nitro PAHs have also been demonstrated to bind cellular DNA in bacteria (67-73) and mammalian cells (74-77), to inhibit preferentially the growth of repair-deficient bacteria (78), to have recombinogenic activity in yeast (66,79-80) and to induce tumors in experimental animals (Table II). 

Metabolism and genetic toxicity have been reported to differ with the isomer of nitro-toluene. p-Nitrotoluene was not mutagenic in bacterial assays, but it did increase sister chromatid exchange frequencies and chromosomal aberrations in vitro-, in vivo it did not increase the frequency of micronuclei in bone marrow of treated rodents. Similar findings were reported for the ortho isomer, except that it did not induce chromosomal aberrations in vitro. Only the ortho isomer induces DNA excision repair in the in vivo-in vitro hepatocyte unscheduled DNA synthesis assay. Furthermore, ort/jo-nitrotoluene binds to hepatic DNA to a much greater extent than meta- or para-nitrotoluene, and investigators suggest that it may act similarly to the rodent hepatocarcino-gen 2,6-dinitrotoluene. ... 

Toxaphene has been found to be genotoxic in a number of assays. It was mutagenic in Sal-Ttimella typhimurium, and increased the frequency of sister chromatid exchanges in cell culture. In one study toxaphene-exposed individuals had a higher incidence of chromosomal aberrations in lymphocytes than controls. However, in vivo toxaphene did not bind to DNA or produce dominant lethal mutations. ... 

Ethylene dibromide induced gene mutations, sister chromatid exchanges, chromosomal aberrations and cell transformation in animal cells. It induced mutations in two human lymphoblastoid cell lines, AHH-1 and TK6 in the absence of exogenous metabolic activation. Administration of radiolabelled ethylene dibromide to Wistar rats and BALB/c mice resulted in binding to DNA, RNA and proteins. [The nature of the binding was not characterized.]... 

Sister chromatid cohesion is primarily established by the cohesin complex (23). The cohesin complex is a multiprotein complex that contains the structural maintenance of chromosomes (SMC) family of proteins (24). SMC proteins contain the Walker A motif at their N-termini and the Walker B motif at their C-termini (Fig. 2a). These motifs are brought together by an intramolecular coiled-coil domain to form a functional ATPase domain, which is similar to other ATP-binding cassette (ABC) ATPases, such as RAD50 (25). SMC proteins... 

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