{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:22:17Z","timestamp":1789363337812,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T00:00:00Z","timestamp":1392336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by <jats:italic>in vivo<\/jats:italic> incorporation of [<jats:sup>3<\/jats:sup>H]methyl thymidine. A more recent non\u2010isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation <jats:italic>in vivo<\/jats:italic>. To further improve the utility of this assay, we developed an <jats:italic>ex vivo<\/jats:italic> BrdU labeling procedure eliminating the need for <jats:italic>in vivo<\/jats:italic> injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak\/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non\u2010sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the <jats:italic>in vivo<\/jats:italic> LLNA:BrdU\u2010enzyme\u2010linked immunosorbent assay labeling procedure. We also used the <jats:italic>ex vivo<\/jats:italic> BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and <jats:italic>cis<\/jats:italic>\u2010diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC<jats:sub>2<\/jats:sub> values. We conclude that this <jats:italic>ex vivo<\/jats:italic> BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.<\/jats:p>","DOI":"10.1002\/jat.2983","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T05:14:53Z","timestamp":1392614093000},"page":"29-40","source":"Crossref","is-referenced-by-count":18,"title":["Development and utilization of an <i>ex vivo<\/i> bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers"],"prefix":"10.1002","volume":"35","author":[{"given":"W. 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