Je. Ploski et Pd. Aplan, Characterization of DNA fragmentation events caused by genotoxic and non-genotoxic agents, MUT RES-F M, 473(2), 2001, pp. 169-180
Citations number
34
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Leukemic cells have been shown to generate several classes of DNA fragments
after treatment with cytotoxic cancer chemotherapy agents. However, it is
unclear which of these fragmentation events are a direct effect of DNA-dama
ging chemotherapy agents, and which fragmentation events are caused by down
stream processes. such as apoptosis. We have performed a detailed analysis
of DNA fragmentation events which occur following cytotoxic chemotherapy in
four representative leukemic cell lines (HL-60, Jurkat, K562, and Molt-4).
We used a DNA topoisomerase II inhibitor (etoposide), an alkylating agent
(melphalan), a nucleoside analog (cytosine arabinoside), and a non-genotoxi
c agent (N-methylformamide) to induce cell death. We studied high molecular
weight and low molecular weight DNA fragmentation events, as well as the s
pecific cleavage of the MLL breakpoint cluster region (bcr). The DNA fragme
nts produced at late time points were largely independent of the agents use
d. while those generated at earlier time points showed dear differences in
terms of fragment size and relative abundance, depending on the agent used.
In addition. there were clear differences between cell lines in terms of s
ize, relative abundance, and rate at which DNA fragments were produced by t
reatment with the same agents. We think that this survey documents the impo
rtance of studying several different cell lines. time points, and assays be
fore reaching conclusions about the types of DNA fragments produced during
treatment with cytotoxic agents. and provides a useful framework for studyi
ng a wide range of DNA fragments produced by cytotoxic agents. Published by
Elsevier Science B.V.