{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T23:03:34Z","timestamp":1698447814731},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,4,22]],"date-time":"2008-04-22T00:00:00Z","timestamp":1208822400000},"content-version":"vor","delay-in-days":6686,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[1990,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In previously described activation systems [Clive D, Spector JFS (1975): Mutat Res 31:17\u201429] for the mouse lymphoma mutation assay the cofactor isocitrate is rapidly exhausted and the resultant loss of NADPH can halt metabolic processes. Presented here are data obtained with a non\u2010toxic balance of NADP (1.4 mg\/ml), isocitrate (6.0 mg\/ml), and S9 (\u22644%) in Fischer's medium which produces a more stable supply of the required cofactors. By spectrophotometric analysis, the molar concentration of NADPH remains at \u226550% or more of the maximum over the usual 4\u2010hr treatment period. Accompanying this increase in NADPH duration was increased toxicity and mutant frequency at most doses among cells treated with the reference mutagens 3\u2010methylcholanthrene (MCA), 2\u2010acetylamofluorene (AAF), benzo(a)pyrene(BAP),9,10\u2010dimethyl\u20101,2\u2010benzanthracene (DMBA), or cyclophosphamide (CPA), but not with dimethylnitrosamine (DMN)\u2010possibly a reflection of the single enzyme mediated step in the metabolism of this chemical. These observations also suggest that results attributed to varying the amounts of S9 in an activation mixture may be due to suboptimal cofactor levels and further emphasize the need to maintain sufficient NADPH exposure to evaluate the effects of metabolic enzyme levels or compare the relative activities of analogous chemicals.<\/jats:p>","DOI":"10.1002\/em.2850160411","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T18:13:12Z","timestamp":1172081592000},"page":"311-319","source":"Crossref","is-referenced-by-count":13,"title":["Development of an optimal S9 activation mixture for the L5178Y TK<sup>+\/\u2212<\/sup> mouse lymphoma mutation assay"],"prefix":"10.1002","volume":"16","author":[{"given":"Jenness B.","family":"Majeska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale W.","family":"Matheson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. E.","family":"Holden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,4,22]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(82)90019-X"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(75)90046-1"},{"key":"e_1_2_1_4_1","first-page":"371","article-title":"Rates of pentose cycle flux in perfused rat liver. Evaluation of the role of reducing equivalents from the pentose cycle for mixed\u2010function oxidation","volume":"28","author":"Belinsky SA","year":"1985","journal-title":"Mol Pharmacol"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(75)90059-X"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(79)90195-7"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(79)90058-7"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860060407"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(82)90021-5"},{"key":"e_1_2_1_10_1","first-page":"68","article-title":"Optimization of an S9 activation mixture for the L5178Y Tk +\/\u2010 mouse lymphoma mutation assay","volume":"9","author":"Majeska JB","year":"1987","journal-title":"Environ Mol Mutagen"},{"key":"e_1_2_1_11_1","first-page":"10","article-title":"Optimisation of a metabolic activation system for use in the mouse lymphoma L5178Y tk + tk\u2010 mutation system","volume":"7","author":"McGregor DB","year":"1985","journal-title":"Environ Mol Mutagen"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/3.6.485"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bk-1981-0174.ch001"},{"key":"e_1_2_1_14_1","first-page":"61","article-title":"Design principles for S9 activation of chemicals in the L5178Y forward mutation assay","volume":"7","author":"Novak JM","year":"1985","journal-title":"Environ Mol Mutagen"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(84)90079-4"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(87)90080-7"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0020-711X(85)90250-2"},{"key":"e_1_2_1_18_1","first-page":"106","article-title":"Validation of cofactor proportions for use of RPMI\u20101640 in assessing the mutagenicity of promutagens in the L5178Y mouse lymphoma forward mutation assay","volume":"11","author":"Tregerman L","year":"1988","journal-title":"Environ Mol Mutagen"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fem.2850160411","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.2850160411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T01:20:04Z","timestamp":1698024004000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.2850160411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,1]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1990,1]]}},"alternative-id":["10.1002\/em.2850160411"],"URL":"https:\/\/doi.org\/10.1002\/em.2850160411","archive":["Portico"],"relation":{},"ISSN":["0893-6692","1098-2280"],"issn-type":[{"value":"0893-6692","type":"print"},{"value":"1098-2280","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,1]]}}}