TY - JOUR
T1 - Effect of 1-β-D-arabinofuranosylcytosine (ara-C) on nuclear topoisomerase II activity and on the DNA cleavage and cytotoxicity produced by 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and etoposide in m-AMSA-sensitive and -resistant human leukemia cells
AU - Bakic, Milorad
AU - Chan, Diana
AU - Andersson, Borje S.
AU - Beran, Miloslav
AU - Silberman, Lynn
AU - Estey, Elihu
AU - Ricketts, Laurie
AU - Zwelling, Leonard A.
N1 - Funding Information:
* This work was supported by PHS Grants CA40090 (L.A.Z.1 and CA39809 (to Dr. Emil J. Freireichl awarded iy the ‘National Can&r Institute, by Grand CH-324 (L.A.Z.) awarded by the American Cancer Society, by a grant from the Leukemia Research Foundation, Inc. (E.E.), and by a gift to the M. D. Anderson Annual Fund for the Chemotherapy Research Program by Mr. Henry C. Beck, Jr., of Dallas, TX. t To whom correspondence should be addressed: Department of Medical Oncology, MD Anderson Hospital and Tumor Institute, Box 52,6723 Bertner Ave., Houston, TX 77030. $ Abbreviations: m-AMSA, 4’-(9_acridinylamino)-methanesulfon-~-anisidide; VP-l& etoposide; ara-C, l-FE_ D-arabinofuranosylcytosine; SDS, sodium dodecyl sulfate; D,, dose increment that reduces survival by a factor of l/e; k, kinetoplast; EGTA, ethyleneglycolbis(aminoethylether)tetra-acetate; and PMSF, phenylmethyfsulfonyl fluoride.
PY - 1987/12/1
Y1 - 1987/12/1
N2 - The ability of a noncytotoxic dose of ara-C to modulate the amount of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA)- or etoposide-induced topoisomerase II-mediated DNA cleavage and cytotoxicity was examined in m-AMSA-sensitive and -resistant HL-60 human leukemia cells. Ara-C pretreatment (0.1 μM × 48 hr) sensitized m-AMSA-sensitive cells to the cytotoxicity and DNA cleavage produced by both m-AMSA and etoposide. The actions of m-AMSA in the m-AMSA-resistant cells were affected minimally by ara-C. By contrast, ara-C enhanced etoposide-induced DNA cleavage and, to an even greater extent, etoposide-induced cytotoxicity in m-AMSA-resistant cells. These cells were only minimally cross-resistant to etoposide. Ara-C did not affect the cellular uptake of m-AMSA or etoposide, the amount of 0.35 M NaCl-extractable nuclear topoisomerase II activity from either cell line, or the ability of this enzyme activity to covalently bind to DNA in the presence of the drugs. m-AMSA- and etoposide-induced DNA cleavage is thought to result from drug-induced stabilization of a topoisomerase II-DNA complex. The ability of ara-C to modulate this effect and associated cytotoxicity appears to be mediated by the effects of ara-C on cellular targets other than topoisomerase II but which are important to topoisomerase II-mediated events, such as protein-associated DNA cleavage. A good candidate for such a target may be cellular chromatin.
AB - The ability of a noncytotoxic dose of ara-C to modulate the amount of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA)- or etoposide-induced topoisomerase II-mediated DNA cleavage and cytotoxicity was examined in m-AMSA-sensitive and -resistant HL-60 human leukemia cells. Ara-C pretreatment (0.1 μM × 48 hr) sensitized m-AMSA-sensitive cells to the cytotoxicity and DNA cleavage produced by both m-AMSA and etoposide. The actions of m-AMSA in the m-AMSA-resistant cells were affected minimally by ara-C. By contrast, ara-C enhanced etoposide-induced DNA cleavage and, to an even greater extent, etoposide-induced cytotoxicity in m-AMSA-resistant cells. These cells were only minimally cross-resistant to etoposide. Ara-C did not affect the cellular uptake of m-AMSA or etoposide, the amount of 0.35 M NaCl-extractable nuclear topoisomerase II activity from either cell line, or the ability of this enzyme activity to covalently bind to DNA in the presence of the drugs. m-AMSA- and etoposide-induced DNA cleavage is thought to result from drug-induced stabilization of a topoisomerase II-DNA complex. The ability of ara-C to modulate this effect and associated cytotoxicity appears to be mediated by the effects of ara-C on cellular targets other than topoisomerase II but which are important to topoisomerase II-mediated events, such as protein-associated DNA cleavage. A good candidate for such a target may be cellular chromatin.
UR - https://www.scopus.com/pages/publications/0023492463
UR - https://www.scopus.com/pages/publications/0023492463#tab=citedBy
U2 - 10.1016/0006-2952(87)90563-6
DO - 10.1016/0006-2952(87)90563-6
M3 - Article
C2 - 2825713
AN - SCOPUS:0023492463
SN - 0006-2952
VL - 36
SP - 4067
EP - 4077
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 23
ER -