The reverse transcriptase inhibitor 3'-azido-deoxythymidine (AZT) has
previously been shown to be incorporated into specific regions near th
e telomeres and centromeres of Chinese hamster ovary cell chromosomes.
Our investigation of the effects of AZT on chromosome stability has l
ed to the discovery of a high frequency amplification of telomere-like
centromeric DNA. The amplified structures, when analyzed cytogenetica
lly, appear as tandem arrays of tightly clustered blocks of centromeri
c repeats containing telomeric sequences (TTAGGG)(n). There were 5-13
blocks of amplified DNA per structure. These structures form rapidly w
ithin one or two cell cycles and can be observed with an incidence as
high as 2%. Because the amplification was so rapid, we tested whether
the amplification structures could be the result of aberrant overrepli
cation by analyzing BrdU incorporation. Our results indicate that the
amplified DNA does not undergo abnormal replication during its formati
on, but appears to form from existing centromeric regions. We propose
a model that involves the excision of multiple centromeric DNA regions
from other chromosomes and their relocalization to a new site.