{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:12:40Z","timestamp":1758280360970},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":9623,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1978,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxyurea is an excellent selective agent for obtaining drug\u2010resistant mutants. At a frequency of approximately 1 \u00d7 10<jats:sup>\u22125<\/jats:sup> it was possible to select, in a single step, colonies that exhibited significant resistance to the cytotoxic effects of the drug. These hydroxyurea\u2010resistant cell lines maintained their resistant phenotype after extensive cultivation in the absence of the drug. Reconstruction experiments indicated that the expression of hydroxyurea\u2010resistance and the frequency of drug\u2010resistant colonies was independent of cell densities up to 5 \u00d7 10<jats:sup>5<\/jats:sup> cells per 100\u2010mm selection plate. Luria\u2010Delbr\u00fcck fluctuation analyses indicated that the appearance of hydroxyurea\u2010resistant cells in wild type populations occurred spontaneously and at a rate of 4.8 \u00d7 10<jats:sup>\u22126<\/jats:sup> per cell per generation in the presence of 0.33 mM drug. Studies with the mutagen, ethyl methane sulfonate indicated that it was capable of increasing the frequency of hydroxyurea\u2010resistant cells by a factor of approximately 10. Also, cell\u2010cell hybridization experiments showed that hydroxyurea\u2010resistance behaves as a dominant or codominant trait and that hydroxyurea\u2010resistance was a useful new genetic marker for selection of somatic cell hybrids. Furthermore, similar to many other drug\u2010resistant cell lines hydroxyurea\u2010resistant cells were found to exhibit an altered sensitivity to a number of non\u2010selective agents (guanazole, N\u2010carbamoyloxyurea, formamidoxime, and hydroxyurethane). Except for guanazole these compounds are structurally very similar to hydroxyurea and may be expected to have similar modes of action. The results presented in this paper support the view that hydroxyurea\u2010resistance is expressed as a normal genetic trait and is a useful genetic marker for somatic cell genetic studies.<\/jats:p>","DOI":"10.1002\/jcp.1040970108","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T17:01:31Z","timestamp":1109437291000},"page":"73-85","source":"Crossref","is-referenced-by-count":22,"title":["Genetic characterization of hydroxyurea\u2010resistance in chinese hamster ovary cells"],"prefix":"10.1002","volume":"97","author":[{"given":"William H.","family":"Lewis","sequence":"first","affiliation":[]},{"given":"Jim A.","family":"Wright","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(75)90202-X"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(74)90149-4"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(77)90098-7"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01538961"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60975-6"},{"key":"e_1_2_1_7_1","first-page":"60088","volume-title":"A Laboratory Guide to the Mycoplasm of Human Origin","author":"Crawford Y.","year":"1968"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(72)90066-8"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01542629"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(74)90180-8"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00393992"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01538963"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.7.1516"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040780204"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/jnci\/52.6.1811","article-title":"Comparative frequency of dominant and recessive markers for drug resistance in Chinese hamster cells","volume":"52","author":"Harris M.","year":"1974","journal-title":"J. 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