DNA-PK ELISA Kit

Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly (ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the Slack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radio sensitize. Further, PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed resolution of RAD51 foci compared with control cells. However, only PARG inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK) and perturbed mitotic progression. This suggests that PARG has additional functions in the cell compared with inhibition of PARP1/2/3, likely via reversal of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose) (PAR) has a different consequence to inhibiting PAR addition. Overall, our data are consistent with previous genetic findings, reveal new insights into the function of PAR metabolism following IR and demonstrate for the first time the therapeutic potential of PARG inhibitors as radiosensitizing agents.

Background: Managing and recycling electronic waste (e-waste), while useful and necessary, has resulted in significant contamination of several environments in China. The area around Tianjin, China has become one of the world's largest e-waste disposal centers, where electronics are processed by manually disassembly or burning, which can result in serious exposure of workers to a multitude of toxicants. Objective: The present study assessed potential genomic damage in workers involved in recycling e-waste. Methods: To detect cytogenetic and DNA damage, chromosomal aberrations (CA), cytokinesis blocking micronucleus (CBMN) and the comet assay were performed. Concentrations of some trace elements, markers of oxidative stress and polychlorinated biphenyls (PCBs) in whole blood or serum were measured, and relationships among the markers described above, age, and duration of exposure were analyzed. The profiles of expression of genes in lymphocytes in peripheral blood were assessed to determine the status of the regulation of genes involved in genome stability. Results: Concentrations of 28 PCB congeners in the whole blood of the exposed group were significantly (P < 0.001) greater than those in the control individuals. Frequency of CA (8.01%) and CBMN (26.3%) in lymphocytes and the level of DNA damage in the lymphocytes and spermatozoa of the exposed men were also significantly (P < 0.0001) greater than those of the controls. There were significant relationships between CA, CBMN, DNA damage and duration of exposure. Concentrations of malondialdehyde (MDA) and lead (Pb) in the blood serum were significantly greater, but activities of superoxide dismutase (SOD), glutathione (GSH) and concentrations of calcium (Ca) and magnesium (Mg) were lower in the serum of the exposed men. MDA, Pb, Ca and Mg were associated with the duration of exposure to handling e-waste. In males involved in handling of e-waste, there were 13 genes - ATM, ATR, ABL1, CHEK1, CHEK2, GADD45A, CDK7, GTSE1, OGG1, DDB1, PRKDC, XRCC1 and CCNH - for which expression of mRNA was up-regulated and 7 genes - BRCA1, GTF2H1, SEMA4A, MRE11A, MUTYH, PNKP and RAD50 - for which the expression of mRNA was down-regulated. Conclusions: A strong correlation between indicators of damage of DNA, which could result in instability of the genome, and duration of processing e-waste was observed. If proper procedures are not followed, there are significant risks to the health of the individuals involved in such activities.