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.

The effect of low-level 60-Hz electromagnetic fields on human lymphoid cells: II. Sister-chromatid exchanges in peripheral lymphocytes and lymphoblastoid cell lines

Abstract: Dividing human peripheral lymphocytes from 10 normal adults (5 males and 5 females) as well as lymphoid cell lines from patients with the chromosomal instability syndromes were exposed to low-level 60-Hz sinusoidal electromagnetic fields (EMF). The current density of the electrical field was 30 microA/cm2 while the strength of the magnetic field was either 1 or 2 gauss. The cytological endpoints measured included the frequency of sister-chromatid exchanges per chromosome; the distribution of first-, second-, and third-division cells and chromosome breakage (lymphoblastoid cells only). No statistically significant differences, indicative of EMF effects were observed between the treated and control cells regarding SCE frequency, cell cycle progression or chromosome breakage.

Genotoxic effects induced by formaldehyde in human blood and implications for the interpretation of biomonitoring studies.

Abstract: Formaldehyde (FA) was tested for its genotoxicity in human blood cultures. We treated blood samples at the start of the culture to follow FA-induced DNA damage (DNA-protein crosslinks, DPX), its repair and its genetic consequences in form of sister chromatid exchanges (SCE) and micronuclei (MN). Our results clearly indicate that DPX (determined by the comet assay) are induced at FA concentrations of > or =25 microM. DPX induced by FA concentrations up to 100 microM are completely removed before lymphocytes start to replicate. SCE are induced at concentrations >100 microM parallel to the induction of cytotoxicity (measured as reduction of the replication index). MN were not induced by FA concentrations up to 250 microM (the highest analyzable concentration) added at the start of the blood cultures in the cytokinesis-block micronucleus (CBMN) test. FA-induced cytotoxicity (measured as reduction of the nuclear division index) possibly prevented division of damaged cells. MN were only significantly induced in human blood when proliferating cells were exposed to FA during the last cell cycle before preparation. Several human biomonitoring studies reported increased frequencies of SCE and MN in lymphocytes of subjects exposed to FA. Our results characterize the genotoxic potential of FA in cultured lymphocytes and lead to the conclusion that cytogenetic effects of FA are very unlikely to occur in blood cultures of FA-exposed subjects.

Inactivation of Human MAD2B in Nasopharyngeal Carcinoma Cells Leads to Chemosensitization to DNA-Damaging Agents

Abstract: Rev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and gamma-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene.