title: A novel class of unstable 6-thioguanine-resistant cells from dog and human kidneys.
abstract: Thioguanine-resistant primary clones were grown from single cell suspensions obtained from dog and human kidneys by enzymatic digestion. In medium containing a relatively high concentration (10 micrograms/ml) of thioguanine, thioguanine-resistant primary clones arose from each source at frequencies ranging from 10(-4) to 10(-5). A reduction in total hypoxanthine uptake was found in the thioguanine-resistant primary clones which had developed in thioguanine medium, consistent with a reduction in hypoxanthine phosphoribosyltransferase activity. When these thioguanine-resistant primary clones were subsequently grown in the absence of thioguanine and assayed for the thioguanine-resistant phenotype and hypoxanthine phosphoribosyltransferase activity, it was found that most were now thioguanine-sensitive and yielded cell-free extracts with substantial amounts of hypoxanthine phosphoribosyltransferase activity. In contrast, thioguanine-resistant human clones grown continuously in the presence of thioguanine yielded cell-free extracts with little or no detectable hypoxanthine phosphoribosyltransferase activity. Southern blot analysis demonstrated no structural alterations in the hypoxanthine phosphoribosyltransferase gene in thioguanine-resistant primary human kidney clones. These results suggest that a novel mechanism(s) for thioguanine resistance and the control of hypoxanthine phosphoribosyltransferase expression may occur in dog and human kidney cells.
authors.affiliation: Department of Pathology, University of Washington, Seattle 98195.
authors.forename: M S
authors.initials: MS
authors.lastname: Turker
authors.forename: R J
authors.initials: RJ
authors.lastname: Monnat
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: P A
authors.initials: PA
authors.lastname: Johnston
authors.forename: C E
authors.initials: CE
authors.lastname: Ogburn
authors.forename: R E
authors.initials: RE
authors.lastname: Weller
authors.forename: J F
authors.initials: JF
authors.lastname: Park
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D004351:Drug Resistance; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D007668:Kidney / Q000166:cytology*; D012641:Selection, Genetic; D013866:Thioguanine / Q000494:pharmacology*
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine