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.

Transient ATM Kinase Inhibition Disrupts DNA Damage–Induced Sister Chromatid Exchange

Abstract: Cells derived from ataxia telangiectasia (A-T) patients exhibit defective cell cycle checkpoints because of mutations in the gene encoding ATM (ataxia telangiectasia mutated). After exposure to ionizing radiation (IR), A-T cells exhibit sensitivity to IR-induced cellular damage that results in increased chromosome aberrations and cell death (radiosensitivity). ATM is a member of a family of kinases that become activated in response to DNA damage. We showed that even transient inhibition of ATM kinase for 1 hour, initiated 15 minutes after cellular irradiation, resulted in an accumulation of persistent chromosome aberrations and increased cell death. Using reversible inhibitors of DNA-PK (DNA-dependent protein kinase), another kinase involved in responding to DNA damage, and ATM, we showed that these two kinases acted through distinct DNA repair mechanisms: ATM resolved DNA damage through a mechanism involving sister chromatid exchange (SCE), whereas DNA-PK acted through nonhomologous end joining. Furthermore, because DNA damage–induced SCE occurred in A-T fibroblasts that lack functional ATM protein, and the inhibitors of ATM kinase had no effect on DNA damage–induced SCE in A-T fibroblasts, we showed that the consequences of short-term inhibition of the kinase activity of ATM and adaptation to ATM protein disruption were distinct. This suggests that A-T fibroblasts have adapted to the loss of ATM and have alternative mechanisms to initiate SCE.

Sister chromatid exchanges in human leukocyte chromosomes: spontaneous and induced frequencies in early- and late-proliferating cells in vitro.

Abstract: Human leukocyte cultures were pulse-treated with the trifunctional alkylating mutagen trenimon in a final concentration of 10-7M for 15–20 h after culture start, i.e., in the G1 phase of the cell cycle. At 24 h after culture start bromodeoxyuridine (BUdR) was added to the trenimon-treated cultures and to several untreated cultures running in parallel. The series treated with BUdR only and the series treated with BUdR+trenimon were each used to prepare two cultures at different culture times. Mitoses were collected during consecutive intervals of 12 h from 30 h up to 102 h after culture initiation by colcemid. For all preparation times (42 h, 54 h, 66 h, 78 h, 90 h, and 102 h) the frequencies of first, second, and third and further mitoses were determined in the BUdR- and in the BUdR+trenimon-treated series. In the trenimon-treated series a clear cell cycle delay was detected as compared with the normal distribution of different types of mitoses found in series treated with BUdR only. Spontaneous and trenimon-induced sister chromatid exchange (SCE) frequencies were determined in second mitoses occurring at 66 h, 78 h, 90 h, and 102 h after culture start. For all these preparation times about six SCE per metaphase were consistently found in BUdR-treated, and about 19 SCE per metaphase in BUdR+trenimon-treated series, indicating a homogeneous sensitivity of early- and late-proliferating cells with respect to the induction of SCE.

Induction of sister chromatid exchanges by cypermethrin and carbosulfan in bone marrow cells of mice in vivo

Abstract: The public health effects of pesticides cannot be denied. However, the undesired effects of chemical pesticides have been recognized as a serious public health concern during the past decades. The present study describes the genotoxic effects of two pesticides, namely cypermethrin and carbosulfan, in a murine test system in vivo. The test parameter used was analysis of sister chromatid exchanges (SCE) in bone marrow cells. Both cypermethrin (5, 10 and 20 mg/kg) and carbosulfan (1.25, 2.5 and 5 mg/kg) induced significant increases in the frequency of SCEs (P < 0.001). However, no significant dose-response correlation could be found for either of the pesticides. Carbosulfan induced a cell cycle delay, as evidenced by an increase in average generation time accompanied by accumulation of cells in the first division cycle, but cypermethrin did not induce any such response. The present study indicates that carbosulfan has a higher potential to cause genetic alterations than cypermethrin in mice and may also pose a mutagenic risk to human beings.