| Summary: | 碩士 === 國立臺灣師範大學 === 生物學系 === 84 === In the cells , the topology of DNA is orchestrated by enzyme
known as topoisomerase Topoisomerases are involved in many
aspects of DNA metabolism such as replication ,transcription ,
recombination , and repair reactions . Camptothecin , which
stabolizes the covalent intermediate of topoisomerase I and DNA
is effective , by cytotoxicity , drug for cancer therapy . In
this study , two new kinds oftopoisomerase I inhibitor purified
from the Chinese herbs (Artocarpus heterophyllus ) and synthetic
quinolone derivatives have been demonstrated to be strong
topoisomerase inhibitors by using topoisomerase I relaxation
assay .Increasing the steady-state concentration of their
covalent DNA cleavage complex will convert topoisomerase into
physiological toxins that introducehigh levels of transient
protein-associated breaks in the genome of treatedcells .
Collision of DNA relication forks with cleavable complexes has
been proposed as a mechanism inducing cell death . We have known
that the topoisomerase I inhibitor camptothecin induced
apoptosis ( programmedcell death ) of cells of human
promyelogenous leukemia HL-60 cells .The two new kinds of
topoisomerase I inhibitors that we have identified in this study
, also can induce apoptosis of cell of human promyelogenous
leukemia HL-60 through the following cell features were focused
to characterize the mode cell : [a] Activation of an
endonuclease in apoptoticcells resulted in the formation of low
molecular weight DNA fragmentswhich were confirmed by agarose
gel electrophoresis . [b] Changes in cellular morphology of
apoptotic cells resulted in the early appearanceof shrunken
cells with vacuolated cytoplasma and regions of intensechromatin
staining around the nuclear periphery . By this study , we
hopeto identify the gene products which couple the stimulus of
programmed cancer cell death , and to determine intrinsic
cellular sensitivity( or resistance ) which will be important
targets for new types ofantitumor drugs .
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