PMID- 16705757
OWN - NLM
STAT- MEDLINE
DCOM- 20070808
LR  - 20161124
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 26
IP  - 4
DP  - 2006 Jul-Aug
TI  - Evaluation of an ex vivo murine local lymph node assay: multiple endpoint 
      comparison.
PG  - 333-40
AB  - The local lymph node assay (LLNA) is used to assess the skin sensitization 
      potential of chemicals. In the standard assay, mice are treated topically on the 
      dorsum of both ears with test substance for 3 days. Following 2 days of rest, the 
      initiation of the hypersensitivity response is evaluated by injecting 
      (3)H-thymidine into a tail vein, and then measuring the levels of radioisotope 
      incorporated into the DNA of lymph node cells draining the ears. In the current 
      study, BALB/c mice were treated with the contact sensitizers hexylcinnamic 
      aldehyde (HCA) and oxazolone, and the nonsensitizer methyl salicylate. The 
      proliferative response of lymph node cells was evaluated in an ex vivo assay, in 
      which isolated cells were cultured in vitro with (3)H-thymidine. Treatment of 
      mice with HCA at 5-50% resulted in concentration-related increases in 
      (3)H-thymidine incorporation, with stimulation indices ranging from 3 to 14. Low 
      animal-to-animal variability was seen in three replicate assays testing HCA at 
      25%. As anticipated, the proliferative response induced by the potent sensitizer 
      oxazolone at 0.25% was greater than HCA at all concentrations tested. Stimulation 
      indices of 1.5 and 3 were seen in two independent experiments with methyl 
      salicylate. These equivocal findings were likely due to the irritancy properties 
      of the compound. Importantly, measuring ex vivo (3)H-thymidine incorporation was 
      more sensitive than evaluating lymph node weight and cellularity, and in vitro 
      bromodeoxyuridine incorporation. Furthermore, the results of the ex vivo LLNA 
      were comparable to the standard assay. This study provided evidence that supports 
      the use of an ex vivo LLNA for hazard assessment of contact hypersensitivity.
CI  - Copyright 2006 John Wiley & Sons, Ltd.
FAU - Piccotti, Joseph R
AU  - Piccotti JR
AD  - Worldwide Safety Sciences, Pfizer Global Research and Development, Ann Arbor, MI 
      48105, USA. joseph.piccotti@pfizer.com
FAU - Knight, Stephanie A
AU  - Knight SA
FAU - Gillhouse, Kimberly
AU  - Gillhouse K
FAU - Lagattuta, Mark S
AU  - Lagattuta MS
FAU - Bleavins, Michael R
AU  - Bleavins MR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Irritants)
RN  - 0 (Salicylates)
RN  - 101-86-0 (hexyl cinnamic aldehyde)
RN  - 15646-46-5 (Oxazolone)
RN  - 7864XYD3JJ (Acrolein)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - LAV5U5022Y (methyl salicylate)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Acrolein/administration & dosage/analogs & derivatives/toxicity
MH  - Administration, Topical
MH  - Animals
MH  - Bromodeoxyuridine
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Dermatitis, Contact/*etiology
MH  - Dose-Response Relationship, Drug
MH  - *Endpoint Determination/methods
MH  - Female
MH  - Irritants/administration & dosage/*toxicity
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Organ Size
MH  - Oxazolone/administration & dosage/toxicity
MH  - Reproducibility of Results
MH  - Salicylates/administration & dosage/toxicity
MH  - Thymidine
EDAT- 2006/05/18 09:00
MHDA- 2007/08/09 09:00
CRDT- 2006/05/18 09:00
PHST- 2006/05/18 09:00 [pubmed]
PHST- 2007/08/09 09:00 [medline]
PHST- 2006/05/18 09:00 [entrez]
AID - 10.1002/jat.1145 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2006 Jul-Aug;26(4):333-40. doi: 10.1002/jat.1145.