PubMed · 7442329
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R J Shmookler Reis, S Goldstein, C B Harley. 1980. Is cellular aging a stochastic process?. https://doi.org/10.1016/0047-6374(80)90081-0
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In this work, we shed new light on the highly debated issue of chromatin fragmentation in cryopreserved cells. Moreover, for the first time, we describe replicating cell-specific DNA damage and higher-order chromatin alterations after freezing and thawing. We identified DNA structural changes associated with the freeze-thaw process and correlated them with the viability of frozen and thawed cells. We simultaneously evaluated DNA defects and the higher-order chromatin structure of frozen and thawed cells with and without cryoprotectant treatment. We found that in replicating (S phase) cells, DNA was preferentially damaged by replication fork collapse, potentially leading to DNA double strand breaks (DSBs), which represent an important source of both genome instability and defects in epigenome maintenance. This induction of DNA defects by the freeze-thaw process was not prevented by any cryoprotectant studied. Both in replicating and non-replicating cells, freezing and thawing altered the chromatin structure in a cryoprotectant-dependent manner. Interestingly, cells with condensed chromatin, which was strongly stimulated by dimethyl sulfoxide (DMSO) prior to freezing had the highest rate of survival after thawing. Our results will facilitate the design of compounds and procedures to decrease injury to cryopreserved cells.
Advanced glycation end-products (AGEs) have been reported to be accumulated in dermal skin. However, the role of AGEs in the photoaging of human skin remains unknown, and for this reason, we have examined the interaction between AGEs and ultraviolet A light (UVA) from both the chemical and biological aspects. Previously, we reported that exposing human dermal fibroblasts to UVA in the presence of AGEs that were prepared with bovine serum albumin (BSA) decreased the cell viability due to superoxide anion radical s (.O2(-)) and hydroxyl radicals (.OH) generated by AGEs under UVA irradiation, and active oxygen species are detected with ESR spin-trapping. To identify the active oxygen species in detail and to clarify the cell damaging mechanism, we performed several experiments and the following results were obtained. (1) In ESR spin-trapping, by addition of dimethyl sulfoxide and superoxide dismutase, ESR signals due to .O2(-) -derived DMPO-OOH and .OH-derived DMPO-OH adducts, respectively, were detectable. (2) UVA-irradiated AGEs elevated the lipid peroxide levels in both fibroblasts and liposomes. But the peroxidation in liposomes was inhibited by addition of deferoxamine. (3) Survival of fibroblasts exposed to UVA in the presence of AGEs was elevated by addition of deferoxamine. And finally, (4) survival of fibroblasts was found to be regulated by the level of H2O2. On the basis of these results, we propose a possible mechanism in which AGEs under UVA irradiation generate active oxygen species involving .O2(-), H2O2, and .OH, and the .OH species plays a harmful role in promoting cell damage.
The in vitro cytotoxic potential of six commonly used methacrylate polymers was evaluated using human oral fibroblast cultures with different cell-material contact systems. A tissue culture insert was introduced to test resin-released components. Both acute and delayed cytotoxic effects of resin were quantified by cellular enzymatic and DNA synthetic activities of fibroblasts over a 6-day exposure period. Resin toxicity was material-dependent. Statistical analysis showed that the experimental conditions significantly contributed to the overall toxicity and the cytotoxicity pattern for a given material. DNA synthesis activity of human oral fibroblasts assayed by 3H-thymidine incorporation was more sensitive to resins than cellular enzyme activity, as determined by tetrazolium bromide reduction. However, extended exposure increased the cytotoxicity of all resins, as measured by tetrazolium bromide reduction, which seemed to be a better indicator of the development of resin toxicity than 3H-thymidine incorporation. Removal of the oxygen inhibition layer on resin specimens partially enhanced cell viability, indicating that this surface layer together with other unknown factors contributed to resin toxicity.