TY - JOUR
T1 - Collateral resistance of a dideoxycytidine-resistant cell line to 5-fluoro-2'-deoxyuridine
AU - Agarwal, Ram P.
AU - Han, Tieran
AU - Fernandez, Marilyn
N1 - Funding Information:
This work was supported by the Department of Health and Human Service Grant NIAID AI 29155.
PY - 1999/9/7
Y1 - 1999/9/7
N2 - Exposure of a human lymphocytic cell line, H9 cells, to 0.5 μM and 5.0 μM dideoxycytidine (ddC) resulted in isolation of ddC-resistant H9-ddC0.5w and H9-ddC5.0w cell lines. In addition, these cell lines were also resistant to azidothymidine and had reduced deoxycytidine kinase and thymidine kinase activities. We now show that these cell lines are 4-fold and 2000-fold collaterally resistant to 5-fluoro-2'-deoxyuridine (FdUR), respectively, but not to 5-fluorouracil (FU). Biochemical evaluations show that, compared to the parental cells, the FdUR phosphorylation was reduced to 36.3% and 9.2% and the FdUMP levels were decreased to 48.1% and 1.2% in these cell lines. Taken together, the data suggest that ddC, an antiviral agent, is capable of inducing resistance to FdUR - a drug that is not its analog and which has a different metabolism, target site, and mechanism of action.
AB - Exposure of a human lymphocytic cell line, H9 cells, to 0.5 μM and 5.0 μM dideoxycytidine (ddC) resulted in isolation of ddC-resistant H9-ddC0.5w and H9-ddC5.0w cell lines. In addition, these cell lines were also resistant to azidothymidine and had reduced deoxycytidine kinase and thymidine kinase activities. We now show that these cell lines are 4-fold and 2000-fold collaterally resistant to 5-fluoro-2'-deoxyuridine (FdUR), respectively, but not to 5-fluorouracil (FU). Biochemical evaluations show that, compared to the parental cells, the FdUR phosphorylation was reduced to 36.3% and 9.2% and the FdUMP levels were decreased to 48.1% and 1.2% in these cell lines. Taken together, the data suggest that ddC, an antiviral agent, is capable of inducing resistance to FdUR - a drug that is not its analog and which has a different metabolism, target site, and mechanism of action.
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U2 - 10.1006/bbrc.1999.1270
DO - 10.1006/bbrc.1999.1270
M3 - Article
C2 - 10471381
AN - SCOPUS:0033533415
VL - 262
SP - 657
EP - 660
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -