TY - JOUR
T1 - Absence of tRNA-guanine transglycosylase in a human colon adenocarcinoma cell line
AU - Gündüz, Ufuk
AU - Elliott, Mark S.
AU - Seubert, Patricia H.
AU - Houghton, Janet A.
AU - Houghton, Peter J.
AU - Trewyn, Ronald W.
AU - Katze, Jon R.
N1 - Funding Information:
We thank Felicia Waller for expert technical assistance and Dr. Kathryn Deshpande for critical reading of the manuscript. This work was supported by Grant R-810714-02 from the Environmental Protection Agency; Grants CA 20919, CA 23099, CA 32613 and CA 21765 from the National Cancer Institute; American Lebanese Syrian Associated Charities; Biomedical Research Support Grant RR 05423 to the University of Tennesse, Memphis; and Dr. Preston Dorsett.
PY - 1992/7/7
Y1 - 1992/7/7
N2 - Queuosine (Q), found exclusively in th first position of the anticodons of tRNAAsp, tRNAAsn, tRNAHis and tRNATyr, is synthesized in eucaryotes by a base-for-base exchange of queuine, the base of Q, for guanine at tRNA position 34. This reaction is catalyzed by the enzyme tRNA-guaning transglucosylate (EC 2.4.2.29). We measured the specific release of queuine from Q-5′-phsphate (queuine salvage) and the extent of tRNA Q modification in 6 human tumors carried as xenografts in immune-deprived mice. Q-deficient tRNA was found in 3 of the tumors but it did not correlate with diminished queuine salvage. The low tRNA Q content of one tumor, the HxGC3 colo adenocarcinoma, prompted us to examine a HxGC3-derived cell line, GC3/M. GC3/M completely lacks Q in its tRNA and measurable tRNA-guanine transglycosylase activity; the first example of a higher eucaryotic cell which lacks this enzyme. Exposure of GC3/M cells to 5-azacytidine induces the transient appearance of Q-positive tRNA. This result suggests that at least one allele of the transglycosylase gene in GC3/M cells may have been inactivated by DNA methylation. In clinical samples, we found Q-deficient tRNA in 10 of 46 solid tumors, including 2 of 13 colonic carcinomas.
AB - Queuosine (Q), found exclusively in th first position of the anticodons of tRNAAsp, tRNAAsn, tRNAHis and tRNATyr, is synthesized in eucaryotes by a base-for-base exchange of queuine, the base of Q, for guanine at tRNA position 34. This reaction is catalyzed by the enzyme tRNA-guaning transglucosylate (EC 2.4.2.29). We measured the specific release of queuine from Q-5′-phsphate (queuine salvage) and the extent of tRNA Q modification in 6 human tumors carried as xenografts in immune-deprived mice. Q-deficient tRNA was found in 3 of the tumors but it did not correlate with diminished queuine salvage. The low tRNA Q content of one tumor, the HxGC3 colo adenocarcinoma, prompted us to examine a HxGC3-derived cell line, GC3/M. GC3/M completely lacks Q in its tRNA and measurable tRNA-guanine transglycosylase activity; the first example of a higher eucaryotic cell which lacks this enzyme. Exposure of GC3/M cells to 5-azacytidine induces the transient appearance of Q-positive tRNA. This result suggests that at least one allele of the transglycosylase gene in GC3/M cells may have been inactivated by DNA methylation. In clinical samples, we found Q-deficient tRNA in 10 of 46 solid tumors, including 2 of 13 colonic carcinomas.
KW - 5-Axazytidine
KW - DNA methylation
KW - Human tumor
KW - Queuine
KW - Queuosine
KW - tRNA-guanine transglycosylase
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U2 - 10.1016/0925-4439(92)90139-E
DO - 10.1016/0925-4439(92)90139-E
M3 - Article
C2 - 1378304
AN - SCOPUS:0026736382
SN - 0925-4439
VL - 1139
SP - 229
EP - 238
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 3
ER -