Indexed on: 01 Nov '02Published on: 01 Nov '02Published in: Biogerontology
Human diploid fibroblasts in tissue culture undergo replicative senescence after a finite number of divisions that is characterized by a permanent loss of their dividing potential. However, senescence-like phenotypes, including growth cessation, morphological changes, and appearance of senescence-associated β-galactosidae (SA-gal) activity, can be induced by treating early passage cells with C6-ceramide, H2O2, LY294002, or trichostatin A. While there is convincing evidence that telomere shortening is causally related to replicative senescence, the role of telomere shortening in the chemical-induced premature senescence is unclear. Here we employed a normal human BJ cell strain and its telomerase-transfected counterpart, termed BJ-T cells, to examine whether active telomerase in BJ-T can block or delay the premature senescence induced by various chemicals and, if not, whether telomere shortening still occurs. We found that, although all four chemicals tested could induce growth arrest, and in some cases SA-gal activity, in both BJ and BJ-T cells, only H2O2 clearly caused an irreversible loss of dividing potential. H2O2 treatment did not inhibit the cellular telomerase activity, nor did it cause any appreciable telomere shortening in BJ-T cells. These results suggest that oxidative stress and other chemical reagents can target at sites unrelated to the telomere-associated clocking mechanism. Alternatively these chemicals may bypass the telomere length maintenance machinery and target at its downstream sites.