Sister chromatid exchange

About: Sister chromatid exchange is a research topic. Over the lifetime, 3187 publications have been published within this topic receiving 90029 citations. The topic is also known as: replication-born DSB repair by SCE & GO:1990414.

Statistical analysis of high SCE frequency cells in human lymphocytes.

Abstract: The existence of a subpopulation of lymphocytes in which genetic damage persists was identified in experiments on rabbits injected with low levels of mitomycin C. This led to the suggestion that an important parameter to quantify after exposure to a possibly harmful agent may be the proportion of cells with high sister chromatid exchange (SCE) frequency, i.e., high frequency cells (HFCs). In the research reported here we describe the statistical properties of HFCs, particularly their utility in detecting low levels of genetic damage which may be undetected by a simple t-test comparing the means of two samples of SCEs.

Comparative mutagenic and genotoxic effects of three antimalarial drugs, chloroquine, primaquine and amodiaquine

Abstract: Comparative mutagenic and genotoxic effects of three antimalarial drugs, chloroquine, primaquine and amodiaquine, were assessed in the Ames mutagenicity assay (in strains TA97a, TA100, TA102 and TA104) and in vivo sister chromatid exchange (SCE) and chromosome aberration (CA) assays in bone marrow cells of mice. These are the most commonly used antimalarial drugs available at present throughout the world. The results of the bacterial mutagenicity assays showed a very weak mutagenic effect of all three drugs in Salmonella strains TA97a and TA100 both with and without S9 mix and in TA104 only with S9 mix. The results of the in vivo SCE and CA assays indicate that these three drugs are genotoxic in bone marrow cells of mice.

Cellular resistance to chloroethylnitrosoureas, nitrogen mustard, and cis-diamminedichloroplatinum(II) in human glial-derived cell lines.

Abstract: We investigated the cytotoxic and cytogenetic effects of 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea on five cell lines established from human glioma biopsy specimens. Compared to the sensitive cell line SF-126, SF-188 cells are 3- to 6.5-fold more resistant to the cytotoxic effects and 8- to 14-fold more resistant to the induction of sister chromatid exchanges. Cytotoxic effects and induction of sister chromatid exchanges are intermediate for SF-210 and SF-295 cell lines compared with SF-126 and SF-188. There is a good correlation between susceptibility to the cytotoxic effects and formation of DNA interstrand cross-links for cells treated with 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea . We quantitated the extent of repair of O6-methylguanine after treatment of these cell lines with [3H]methylnitrosourea. SF-126 cells showed no detectable repair of O6-methylguanine, SF-210 and SF-295 had intermediate levels of repair, and SF-188 had very high levels of repair. We conclude that the cellular capacity to repair O6-chloroethylguanine adducts in DNA, which is reflected in the methyl repair process, is an important factor in determining cytotoxic response, and that increased repair of O6-chloroethylguanine decreases cytotoxicity and causes fewer sister chromatid exchanges and DNA interstrand cross-links to form in cells treated with chloroethylnitrosoureas. We studied the effects of cis-diamminedichloroplatinum(II) and nitrogen mustard in these cell lines. cis-Diamminedichloroplatinum(II) was equally cytotoxic and induced the same number of sister chromatid exchanges and DNA interstrand cross-links in all five cell lines. In contrast to the results obtained by treatment with chloroethylnitrosoureas, SF-126 cells treated with nitrogen mustard are 7.6-fold more resistant to the cytotoxic effects, 2-fold more resistant to the induction of sister chromatid exchanges, and 3-fold more resistant to the induction of DNA interstrand cross-links than are SF-188 cells. The results of this investigation with five human glial-derived cell lines clearly indicate that the molecular mechanisms of cellular resistance to alkylating chemotherapeutic agents are highly specific. Cellular resistance to chloroethylnitrosoureas does not result in cross-resistance to nitrogen mustard or cis-diamminedichloroplatinum(II).

Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2.

Abstract: Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (CA), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway.