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. 2000 Aug;35(5):553-71.
doi: 10.1016/s0531-5565(00)00108-x.

Senescence-like changes induced by hydroxyurea in human diploid fibroblasts

E J Yeo  1 , Y C Hwang, C M Kang, I H Kim, D I Kim, J S Parka, H E Choy, W Y Park, S C Park
Affiliations

Senescence-like changes induced by hydroxyurea in human diploid fibroblasts

E J Yeo et al. Exp Gerontol. 2000 Aug.

Abstract

Hydroxyurea was found to inhibit the growth of human diploid fibroblasts, which resulted in senescence-like changes both in morphology and replicative potential similar to the replicative senescence. SA-beta-gal activity, a typical characteristic of the replicative senescence was also induced through a long-term treatment of the presenescent cells with 400-800 microgM of hydroxyurea for about 3 weeks. In addition, we determined the levels of cyclin-dependent kinase inhibitors, p21(Waf1) and p16(INK4a), and the p53 tumor suppressor in order to monitor its effect on cell cycle and stress responses. We observed a great induction of both p53 and p21(Waf1), but not of p16(INK4a) in the premature senescent cells. UV-irradiation of the premature senescent cells showed a decreased level of DNA fragmentation presumably ascribed to the reduced activation of stress-activated protein kinases. These results suggest that a chronic hydroxyurea treatment induces the cellular senescence in association with the induction of p53 and p21(Waf1).

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