V. Bemi et al., 6-thioguanine resistance in a human colon carcinoma cell line with unaltered levels of hypoxanthine guanine phosphoribosyltransferase activity, INT J CANC, 82(4), 1999, pp. 556-561
Cell populations resistant to high doses (30 mu M) of 6-thio-guanine (6-TG,
6-TG(r) cells) were selected from a human colon carcinoma cell line, LoVo.
This cell line, which lacks hMSH2, a component of the human mismatch bindi
ng heterodimer hMutS alpha, is resistant to low doses of 6-TG. The level of
activity of hypoxanthine-guanine phosphoribosyltransferase, the enzyme res
ponsible for the phosphoribosylation of the thiopurine, was comparable to t
hat expressed in the parental cells, Mo significant difference was found in
the levels of enzyme activities involved in the conversion of 6-TG or its
derivatives into non-toxic compounds, In contrast, a significant difference
was found in the uptake kinetics of 6-TG in the 2 cell types. Met uptake o
f 6-TG ceased after 100-sec incubation in the 6-TG(r) cells, while it appea
red to continue throughout the 10 min incubation in the wild-type cells, As
a consequence, after IG-min incubation, the total amount of 6-TG taken up
by the parental LoVo cells was approximately 3 times higher than that prese
nt in the 6-TG(r) cells. (C) 1999 Wiley-Liss, Inc.