MAINTENANCE OF TELOMERES IN SV40-TRANSFORMED PRE-IMMORTAL AND IMMORTAL HUMAN FIBROBLASTS

Shortening of telomeres has been hypothesized to contribute to cellula r senescence and may play a role in carcinogenesis of human cells. Fur thermore, activation of telomerase has frequently been demonstrated in tumor-derived and in vitro immortalized cells. In this study, we have assessed these phenomena during the life span of simian virus 40 (SV4 0)-transformed preimmortal and immortal human fibroblasts. We observed progressive reduction in telomere length in preimmortal transformed c ells with extended proliferative capacity, with the most dramatic shor tening at late passage. Telomere lengths became stabilized (or increas ed) in immortal fibroblasts accompanied, in one case, by the activatio n of telomerase. However, an independent immortal cell line that displ ayed stable telomeres did not have detectable telomerase activity. Fur thermore, we found significant telomerase activity in two preimmortal derivatives. Our results provide further evidence for maintenance of t elomeres in immortalized human fibroblasts, but they suggest a lack of causal relationship between telomerase activation and immortalization . (C) 1996 Wiley-Liss, Inc.