Rp. Agarwal et al., Collateral resistance of a dideoxycytidine-resistant cell line to 5-fluoro-2 '-deoxyuridine, BIOC BIOP R, 262(3), 1999, pp. 657-660
Citations number
16
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Exposure of a human lymphocytic cell line, H9 cells, to 0.5 mu M and 5.0 mu
M dideoxycytidine (ddC) resulted in isolation of ddC-resistant H9-ddC0.5w
and H9-ddC5.0w cell lines. In addition, these cell lines were also resistan
t to azidothymidine and had reduced deoxycytidine kinase and thymidine kina
se activities, We now show that these cell lines are 4-fold and 2000-fold c
ollaterally 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. (C) 1999 Acad
emic Press.