Our results show that the presence of healthy cells profoundly modifies the DNA damage response of genotoxically injured cells by a microtubule– and ATM–dependent exchange of healthy mitochondria. We comparatively characterized the DSB repair in target and non–target cell populations under co– and mono–culture conditions. Here, we designed a co–culture model system containing human pancreatic cancer cells and ATMwt as well as ATM −/− fibroblasts, in which genotoxically injured cells were co–cultured with healthy cells upon removal of secreted factors putatively connectable to bystander effects. Remaining is the important and yet open question how healthy cells influence DNA–damaged cells. A variety of signaling molecules such as ATM, nitric oxide (NO) and reactive oxygen species (ROS) have been shown to be relayed through gap junctions between DNA damaged and healthy cells. Upon DSB sensing, ataxia–telangiectasia mutated (ATM) and DNA protein kinase catalytic subunit (DNA–PKcs) phosphorylate numerous substrates including histone H2AX and p53 binding protein 1 (53BP1). Among the various types of DNA damage, DNA double–strand breaks (DSB), as most life–threatening lesions, are repaired through non–homologous end joining (NHEJ) and homologous recombination (HR). Ī prominent process for intercellular communication is known as bystander effect describing a DNA damage response in healthy cells triggered by signals from damaged cells. Limited mitochondrial functionality results from exposure to DNA–damaging agents like ionizing radiation, which is rescued by mitochondria fission and fusion. Under stress conditions, mitochondria often move from one cell to another and between different cell types. Direct communication through cell–cell contact is one of the most succinct ways to exchange information as demonstrated by transfer of small organelles like mitochondria carrying signaling molecules such as RNA. A parameter to evaluate the degree of intramolecular charge transfer, namely bond length ratio, was proposed it exhibited good agreement with solvatochromic shifts and molecular orbital calculations.In multicellular organisms, neighboring cells continuously exchange information for coordinating homeostasis, survival and development. Two types of molecular conformation, which significantly affect the electronic structures, were observed to be dependent on the alkyl chain length.
I 20–3CNQ formed a two-dimensional bilayer structure by π-stacking and self-assembly of the alkyl chains. Most I n–3CNQ derivatives formed face-to-face and/or side-by-side dimeric motifs to cancel net dipole moments. Diverse molecular packing patterns were observed in the crystal structures.
The I n–3CNQ derivatives with long alkyl chains ( n≥6) produced supercooled liquids displaying conspicuous color changes after melting. The melting points of the I n–3CNQ solids decreased with increasing alkyl chain length until reaching a minimum point (95 ☌) at n=18, and then began to gradually increase, indicating self-aggregation of the alkyl chains.
#CPLOT PRO TRANSFER SERIES#
A series of intramolecular charge-transfer compounds comprised of 1-alkyl-3,3-dimethyl-2-methyleneindoline ( I n, donor, n = alkyl chain length 1–8, 10, 14, 16, 18, 20, and 22) and 7,8,8-tricyanoquinodimethane (=2-(4′-cyanomethylene-2′,5′-cyclohexadienylidene)malononitrile (3CNQ), acceptor) moieties linked through a π-bond, I n–3CNQ were prepared, and their structures are discussed.
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