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 mod el of cellular senescence led to the concept that subcytotoxic stresses und er any molecules at subcytotoxic doses, such as molecules under development in the pharmaceutical, cosmetics and food industry, might lead human fibro blasts into a state closely related to in vitro senescence. This concept wa s then experimentally confirmed in vitro. many biomarkers of replicative se nescence of human fibroblasts were found 72 h after their exposure to vario us kinds of stressors used at non-cytotoxic concentrations. This phenomenon has been termed stress-induced premature senescence (SIPS). Moreover, prot eomics studies have revealed that, besides their effects on the appearance of the biomarkers of senescence, sublethal stresses under a variety of stre ssors also lead to long-term specific changes in the expression level of pr oteins which are stress-specific. These changes have been coined the molecu lar scars of stress. The proteins corresponding to these molecular scars ma y be identified using the latest developments in mass spectrometry. This mo del of stress-induced premature senescence may be applied to the toxicologi cal sciences when testing for the potential irreversible long-term effects of molecules on the cell fate.