K. Nakabayashi et al., DECREASE IN AMPLIFIED TELOMERIC SEQUENCES AND INDUCTION OF SENESCENCEMARKERS BY INTRODUCTION OF HUMAN-CHROMOSOME-7 OR ITS SEGMENTS IN SUSM-1, Experimental cell research, 235(2), 1997, pp. 345-353
Introduction of human chromosome 7 by microcell-mediated chromosome tr
ansfer suppresses indefinite division of SUSM-1, an in vitro establish
ed human fibroblast line. This cell line has unusually long telomeric
sequences although it lacks detectable telomerase activity. Thus, we e
xamined whether such telomeric sequences change upon introduction of c
hromosome 7 or its segments. In the microcell hybrids that stopped div
iding by introduction of chromosome 7, the telomeric sequences were fo
und to be lost or markedly diminished. Introduction of various fragmen
ts (2-40 Mb) of chromosome 7 contained in radiation hybrids gave simil
ar results. On the other hand, the telomeric sequences were not altere
d significantly in the unsuppressed hybrids, a revertant of one suppre
ssed clone, or subclones of SUSM-1 used as controls. In the suppressed
microcell hybrids, the distribution of a mortality marker, mortalin,
was changed to the cytosolic type of mortal cells from the immortal ty
pe of perinuclear fibres. Also, senescence-associated P-galactosidase
was induced to a level similar to that of normally senesced diploid fi
broblasts. These results suggest that human chromosome 7 induces senes
cence in SUSM-1 by suppressing its telomere maintenance mechanism, whi
ch does not depend on telomerase. (C) 1997 Academic Press.