Sister-strand exchange

Chromosome breakage may therefore be linked to other mechanisms of mutagenesis in some fundamental manner. The correction of errors involves breakage of the DNA molecule for both the "cut and patch" type of repair and for sister-strand exchange (Fig. 6.46). 

Figure 6.46 Representation of two mechanisms of repair of DNA damage such as ultraviolet light-induced dimerization. The upper line represents cut and patch repair, the lower sister-strand exchange. Thick lines represent newly synthesized DNA. Source From Ref. 12.

The essence of sister-strand exchange is that a single-stranded segment free of any defects is excised from an undamaged strand on the homologous DNA segment at the replication fork and somehow inserted into the gap... 

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)... 

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). 

The term genotoxicity is a broader term and refers to potentially harmful effects on genetic material, which are not necessarily associated with mutagenicity. Thus, tests for genotoxicity include tests, which provide an indication of induced damage to DNA (but not direct evidence of mutation) via effects such as unscheduled DNA synthesis (UDS), sister chromatid exchange (SCE), DNA strand breaks, DNA adduct formation or mitotic recombination, as well as tests for mutagenicity. ... 

In genotoxic assays in vivo treatment induced sister chromatid exchanges in the bone marrow of mice, and DNA strand breakage was induced in the liver and kidney of rats. / vitro aniline was not mutagenic to bacteria and did not cause DNA damage. ... 

In mammalian cells in vitro cobalt compounds have caused DNA strand breaks, sister chromatid exchanges, and aneuploidy, but not chromosomal aberrations. Cobalt salts... 

NaF was not mutagenic in bacterial assays. Although fluoride has been shown to be clas-togenic in a variety of cell types, the mechanism of clastogenicity has been attributed to the effect of fluoride on the synthesis of proteins involved in DNA synthesis and/or repair, rather than direct interaction between fluoride and DNA. In general, there was no effect on sperm morphology or the frequency of chromosomal aberrations, micronuclei, sister chromatid exchange, or DNA strand breaks in rodents treated in vivo. ... 

In genotoxic assays BNA induced unscheduled DNA synthesis in human cells in vitro and chromosomal aberrations, sister chromatid exchanges, DNA strand breaks, and unscheduled DNA synthesis in rodent cells in vitro-, in vivo it formed DNA adducts in bladder and liver cells of dogs. ... 

Larramendy ML, Popescu NC, DiPaolo JA. 1981. Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and Syrian hamster cell strands. Environ Mutagen 3 597-606. 

DNA strand breaks (Comet assay), MCL-5 cells Gene mutation, human TK6 cells in vitro Gene mutation, human AHH-1 cells in vitro Sister chromatid exchange, human lymphocytes in vitro... 

Body fluids from WAG/Rij rats (plasma), sister chromatid exchange, Chinese hamster ovary cells in vitro DNA strand breaks, cross-links or related damage, animal cells in vivo... 

In cultured mammalian cells, acrylonitrile induced DNA strand breakage, gene mutation, sister chromatid exchanges and chromosomal aberrations, but not aneuploidy or unscheduled DNA synthesis in rat hepatocytes, at least if the silver grain counting method was used. [Studies using the less reliable scintillation counting method have not been summarized.] Cell transformation was induced in several test systems and gap-junctional intercellular communication was inhibited in one study with Chinese hamster V79 cells. 

In studies with human cells in vitro, acrylonitrile induced DNA strand breakage in a single study, gene mutations in two studies and sister chromatid exchanges in two of three studies, but not unscheduled DNA synthesis or chromosomal aberrations in single studies. 

Chang, C. M., Hsia, M. T., Stoner, G. D. Hsu, I. C. (1990) Acrylonitrile-induced sister-chromatid exchanges and DNA single-strand breaks in adult human bronchial epithelial cells. Mutat. Res., 241, 355-360... 

Caprolactam treatment in vivo did not increase DNA single-strand breaks in hepatocytes or unscheduled DNA synthesis in spermatocytes of rats, did not induce sister chromatid exchanges, micronuclei or chromosomal aberrations in mouse bone marrow and did not induce morphological abnormalities in mouse sperm. Inconclusive results were reported in two mouse spot test studies for gene mutations. 

---