PMID- 12965128
OWN - NLM
STAT- MEDLINE
DCOM- 20031028
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 191
IP  - 2-3
DP  - 2003 Sep 30
TI  - Assessment of statistic analysis in non-radioisotopic local lymph node assay 
      (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example.
PG  - 259-63
AB  - The murine local lymph node assay (LLNA) is used for the identification of 
      chemicals that have the potential to cause skin sensitization. However, it 
      requires specific facility and handling procedures to accommodate a radioisotopic 
      (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA 
      based on BrdU incorporation to avoid a use of RI. Although this alternative 
      method appears viable in principle, it is somewhat less sensitive than the 
      standard assay. In this study, we report investigations to determine the use of 
      statistical analysis to improve the sensitivity of a non-RI LLNA procedure with 
      alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the 
      alternative non-RI method required HCA concentrations of greater than 25% to 
      elicit a positive response based on the criterion for classification as a skin 
      sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the 
      alternative method were consistent in both experiments and we examined whether 
      the use of an endpoint based upon the statistical significance of induced changes 
      in LNC turnover, rather than an SI of 3 or greater, might provide for additional 
      sensitivity. The results reported here demonstrate that with HCA at least 
      significant responses were, in each of two experiments, recorded following 
      exposure of mice to 25% of HCA. These data suggest that this approach may be more 
      satisfactory-at least when BrdU incorporation is measured. However, this 
      modification of the LLNA is rather less sensitive than the standard method if 
      employing statistical endpoint. Taken together the data reported here suggest 
      that a modified LLNA in which BrdU is used in place of radioisotope incorporation 
      shows some promise, but that in its present form, even with the use of a 
      statistical endpoint, lacks some of the sensitivity of the standard method. The 
      challenge is to develop strategies for further refinement of this approach.
FAU - Takeyoshi, Masahiro
AU  - Takeyoshi M
AD  - Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822, 
      Ishii-machi, Hita-shi, Oita, 8770061, Japan. takeyoshi-masahiro@ceri.jp
FAU - Sawaki, Masakuni
AU  - Sawaki M
FAU - Yamasaki, Kanji
AU  - Yamasaki K
FAU - Kimber, Ian
AU  - Kimber I
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 101-86-0 (hexyl cinnamic aldehyde)
RN  - 7864XYD3JJ (Acrolein)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Acrolein/adverse effects/*analogs & derivatives/*toxicity
MH  - Animals
MH  - Bromodeoxyuridine/metabolism
MH  - *Data Interpretation, Statistical
MH  - Dermatitis, Allergic Contact/*diagnosis/etiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Random Allocation
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
EDAT- 2003/09/11 05:00
MHDA- 2003/10/29 05:00
CRDT- 2003/09/11 05:00
PHST- 2003/09/11 05:00 [pubmed]
PHST- 2003/10/29 05:00 [medline]
PHST- 2003/09/11 05:00 [entrez]
AID - S0300483X03002555 [pii]
AID - 10.1016/s0300-483x(03)00255-5 [doi]
PST - ppublish
SO  - Toxicology. 2003 Sep 30;191(2-3):259-63. doi: 10.1016/s0300-483x(03)00255-5.