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J F Dierick

Publications and source records attributed to J F Dierick.

7 recordsLinked to original sources

Growth kinetics rather than stress accelerate telomere shortening in cultures of human diploid fibroblasts in oxidative stress-induced premature senescence.

WI-38 human diploid fibroblasts underwent accelerated telomere shortening (490 bp/stress) and growth arrest after exposure to four subcytotoxic 100 microM tert-butylhydroperoxide (t-BHP) stresses, with a stress at every two population doublings (PD). After subcytotoxic 160 microM H2O2 stress or five repeated 30 microM t-BHP stresses along the same PD, respectively a 322 +/- 55 and 380 +/- 129 bp telomere shortening was observed only during the first PD after stress. The percentage of cells resuming proliferation after stress suggests this telomere shortening is due to the number of cell divisions accomplished to reach confluence during the first PD after stress.

Cell Division↗

Stress-induced premature senescence as alternative toxicological method for testing the long-term effects of molecules under development in the industry.

No alternative in vitro method exists for detecting the potential long-term genotoxic effects of molecules at subcytotoxic concentrations, in terms of days and weeks after exposure(s) to the molecule tested. A theoretical model of cellular senescence led to the concept that subcytotoxic stresses under any molecules at subcytotoxic doses, such as molecules under development in the pharmaceutical, cosmetics and food industry, might lead human fibroblasts into a state closely related to in vitro senescence. This concept was then experimentally confirmed in vitro: many biomarkers of replicative senescence of human fibroblasts were found 72 h after their exposure to various kinds of stressors used at non-cytotoxic concentrations. This phenomenon has been termed stress-induced premature senescence (SIPS). Moreover, proteomics studies have revealed that, besides their effects on the appearance of the biomarkers of senescence, sublethal stresses under a variety of stressors also lead to long-term specific changes in the expression level of proteins which are stress-specific. These changes have been coined the molecular scars of stress. The proteins corresponding to these molecular scars may be identified using the latest developments in mass spectrometry. This model of stress-induced premature senescence may be applied to the toxicological sciences when testing for the potential irreversible long-term effects of molecules on the cell fate.

Aging, Premature↗

Consideration of heteroduplexes and homoduplexes for the quantification by competitive PCR of human mitochondrial DNA deletions with ageing of tissues and cells.

The purpose of this work was first to construct two internal standards for human mitochondrial DNA mt DNA corresponding respectively to the fragment resulting from the 4,977 bp common deletion (H2del) and a fragment which was never reported to be deleted (H1). Secondly, we wished to consider the possible effect of annealing between the target and corresponding internal standard which forms heteroduplexes. These experiments show that the correction of the number of copies found by competitive PCR by considering the percentage of heteroduplexes allows a more accurate quantification of the number of target copies present in mt DNA samples. The design of internal standards specific to the fragment resulting from other deletions could also help a more accurate quantification of the frequency of other mt DNA deletions as well, and reconsideration of the role of mt DNA deletions in ageing.

Aging↗