PMID- 12750042
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20151119
IS  - 1056-8719 (Print)
IS  - 1056-8719 (Linking)
VI  - 48
IP  - 1
DP  - 2002 Jul-Aug
TI  - A nonradioisotopic endpoint for measurement of lymph node cell proliferation in a 
      murine allergic contact dermatitis model, using bromodeoxyuridine 
      immunohistochemistry.
PG  - 53-61
AB  - INTRODUCTION: The murine local lymph node assay (LLNA) was developed as an 
      alternative to guinea pig models for the assessment of the xenobiotic contact 
      sensitization potential. However, it would be advantageous to have an alternative 
      endpoint to the usual radioisotopic-dependent measures. In the present study, we 
      investigated the development of a nonradioisotopic endpoint for LLNA using 
      immunohistochemistry. METHODS: Female Balb/c mice were treated by the topical 
      application of strong sensitizers, 2,4-dinitrochlorobenzene (DNCB) and toluene 
      diisocyanate (TDI), and a strong irritant, sodium lauryl sulfate (SLS), on the 
      dorsum of both ears once daily for three consecutive days. The proliferation of 
      cells in the auricular lymph node and ears was analyzed by means of the labeling 
      index (LI) of bromodeoxyuridine (BrdU) incorporation into cells. RESULTS: Skin 
      reactions, consisting of increased ear thickness and the presence of inflammatory 
      cell infiltrates, were observed in mice treated with DNCB and TDI. The cell 
      number and the weight of the lymph nodes in the mice treated with the allergens, 
      DNCB and TDI, were increased compared to vehicle control. We observed an increase 
      in the areas of the B220(+) cells in the lymph nodes of mice treated with 
      allergens, as determined by immunohistochemistry. There was an increase in the 
      percentage of B220(+) cells in mice treated with DNCB and TDI compared to the 
      vehicle control, but not in those treated with SLS. Because we observed an 
      increase in the percentage of B cells in the allergen-treated group, we measured 
      the stimulation index (SI) in the cortex and medulla (C+M) of the lymph node. The 
      SI values of the C+M in the lymph nodes of the mice treated with DNCB and TDI 
      were increased more than threefold compared with that of the control. However, 
      the SI of the C+M in the lymph nodes of the mice exposed to 25% SLS was not 
      significantly increased compared to the vehicle control, although the lymph node 
      weight of the SLS group was significantly increased. DISCUSSION: In Balb/c mice, 
      BrdU immunohistochemistry showed its potential use for the identification and 
      differentiation of chemicals with the capacity to induce irritation and 
      sensitization. The results suggest that the measurement of the SI in the cortex 
      and medulla of the lymph node using BrdU immunohistochemistry could provide a 
      useful method to screen irritants and allergens.
FAU - Lee, Jong Kwon
AU  - Lee JK
AD  - Division of Immunotoxicology, Department of Toxicology, Korea Food and Drug 
      Administration, National Institute of Toxicology Research, Seoul 122-704, South 
      Korea. jkleest@kfda.go.kr
FAU - Park, Jae Hyun
AU  - Park JH
FAU - Park, Seung Hee
AU  - Park SH
FAU - Kim, Hyung Soo
AU  - Kim HS
FAU - Oh, Hye Young
AU  - Oh HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Toxicol Methods
JT  - Journal of pharmacological and toxicological methods
JID - 9206091
RN  - 0 (Allergens)
RN  - 0 (Antimetabolites)
RN  - 0 (Irritants)
RN  - 9007-49-2 (DNA)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - *Antimetabolites
MH  - *Bromodeoxyuridine
MH  - Cell Count
MH  - Cell Division/drug effects
MH  - Cell Separation
MH  - DNA/biosynthesis
MH  - Dermatitis, Allergic Contact/*pathology
MH  - Endpoint Determination
MH  - Female
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Irritants/*toxicity
MH  - Lymph Nodes/*cytology/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
EDAT- 2003/05/17 05:00
MHDA- 2003/07/12 05:00
CRDT- 2003/05/17 05:00
PHST- 2003/05/17 05:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2003/05/17 05:00 [entrez]
AID - S1056-8719(03)00021-2 [pii]
AID - 10.1016/S1056-8719(03)00021-2 [doi]
PST - ppublish
SO  - J Pharmacol Toxicol Methods. 2002 Jul-Aug;48(1):53-61. doi: 
      10.1016/S1056-8719(03)00021-2.