{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:33:15Z","timestamp":1774672395864,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":11449,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1973,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wild\u2010type cultured cells of the frog cell line ICR 2A give rise to 5\u2010bromodeoxyridine (BUdR)\u2010resistant colonies only when the selecting concentration of the drug is 5 \u00d7 10<jats:sup>\u22125<\/jats:sup> M or lower. The progeny of these colonies multiply in 10<jats:sup>\u22124<\/jats:sup> M BUdR; resistance is correlated with the absence of a thymidine (TdR)\u2010specific transport reaction with a K<jats:sup>m<\/jats:sup> in the range of 2\u20137 \u00d7 10<jats:sup>\u22124<\/jats:sup> M. All of the TdR transport\u2010deficient (TT\u2010) isolates examined (25) had TdR kinase activity (4% to 100% of wild\u2010type). Variants deficient in TdR kinase activity (5% of wild\u2010type) were obtained by exposing TT\u2010cultures to 10<jats:sup>\u22123<\/jats:sup> M BUdR. The TK \u2010 variants multply continuously in 10<jats:sup>\u22123<\/jats:sup> M BUdR and retain the phenotype after prolonged culture in the absence of the drug. The frequency with which they occur is increased 20 to 50 fold by prior treatment of the culture with ICR 191, an acridine mustard mutagen.<\/jats:p><jats:p>In haploid cells, it would be expected that TK\u2010 variants would arise in equal numbers from wild\u2010type and TT\u2010 cultures if loss TdR kinase occurred independently of loss of the transport reaction. However, wild\u2010type cells give no colonies resistant to 10<jats:sup>\u22123<\/jats:sup> M BUdR under conditions the give 1 to 50 colonies per million TT\u2010 cells. The TT\u2010 phenotype seems to be a required intermediate state in the origin of the TK\u2010 phenotype. Therefore, the TK\u2010 clones described above are unlikely to be products of mutation at a single genetic locus.<\/jats:p>","DOI":"10.1002\/jcp.1040820208","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T18:13:23Z","timestamp":1109441603000},"page":"199-212","source":"Crossref","is-referenced-by-count":30,"title":["Origin of thymidine kinase deficient (TK\u2212) haploid frog cells via an intermediate thymidine transport deficient (TT\u2212) phenotype"],"prefix":"10.1002","volume":"82","author":[{"given":"L.","family":"Lacko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Wittke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Geck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.10.2874"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(69)90567-9"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/genetics\/62.2.359","article-title":"Mammalian cell genetics. 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