Stress-induced premature senescence as alternativetoxicological method for testing the long-term effectsof molecules under development in the industry
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- 作者：Olivier Toussaint ; Patrick Dumont ; Jean-Fran?ois Dierick ; Thierry Pascal ; Christophe Frippiat ; Florence Chainiaux ; Joao-Pedro Magalhaes ; Fran?ois Eliaers and José Remacle
- 关键词：alternative methods ; drug testing ; in vitro toxicology ; irreversible effects ; premature senescence ; stress ; induced ; sublethal stress
- 刊名：Biogerontology
- 出版年：2000
- 出版时间：June 2000
- 年：2000
- 卷：1
- 期：2
- 页码：179-183
- 全文大小：57 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Cell Biology
Geriatrics and Gerontology
Developmental Biology - 出版者：Springer Netherlands
- ISSN：1573-6768
文摘
No alternative in vitro method exists fordetecting the potential long-term genotoxic effects ofmolecules at subcytotoxic concentrations, in terms ofdays and weeks after exposure(s) to the moleculetested. A theoretical model of cellular senescence ledto the concept that subcytotoxic stresses under anymolecules at subcytotoxic doses, such as moleculesunder development in the pharmaceutical, cosmetics andfood industry, might lead human fibroblasts into a stateclosely related to in vitro senescence. Thisconcept was then experimentally confirmed invitro: many biomarkers of replicative senescence ofhuman fibroblasts were found 72 h after theirexposure to various kinds of stressors used at non-cytotoxic concentrations. This phenomenon has beentermed stress-induced premature senescence (SIPS).Moreover, proteomics studies have revealed that,besides their effects on the appearance of thebiomarkers of senescence, sublethal stresses under avariety of stressors also lead to long-term specificchanges in the expression level of proteins which arestress-specific. These changes have been coined themolecular scars of stress. The proteins correspondingto these molecular scars may be identified using thelatest developments in mass spectrometry. This modelof stress-induced premature senescence may be appliedto the toxicological sciences when testing for thepotential irreversible long-term effects of moleculeson the cell fate.