PMID- 15254333
OWN - NLM
STAT- MEDLINE
DCOM- 20050204
LR  - 20220311
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 81
IP  - 2
DP  - 2004 Oct
TI  - Development of a peptide reactivity assay for screening contact allergens.
PG  - 332-43
AB  - Allergic contact dermatitis resulting from skin sensitization is a common 
      occupational and environmental health problem. In recent years, the local lymph 
      node assay (LLNA) has emerged as a practical option for assessing the skin 
      sensitization potential of chemicals. In addition to accurate identification of 
      skin sensitizers, the LLNA can also provide a reliable measure of relative 
      sensitization potency; information that is pivotal in successful management of 
      human health risks. However, even with the significant animal welfare benefits 
      provided by the LLNA, there is still interest in the development of nonanimal 
      test methods for skin sensitization testing. One characteristic of a chemical 
      allergen is its ability to react with proteins prior to the induction of skin 
      sensitization. The majority of chemical allergens is electrophilic and as such 
      reacts with nucleophilic amino acids like cysteine or lysine. In order to 
      determine if reactivity correlates with sensitization potential, 38 chemicals 
      representing allergens of different potencies (weak to extreme) and 
      nonsensitizers were evaluated for their ability to react with glutathione or 
      three synthetic peptides containing either cysteine, lysine, or histidine. 
      Following a 15-min reaction time for glutathione or a 24 h reaction period for 
      the three synthetic peptides, the samples were analyzed by HPLC. UV detection was 
      used to monitor the depletion of glutathione or the peptide following reaction. 
      The results demonstrate that a significant correlation (Spearman correlation) 
      exists between allergen potency and the depletion of glutathione (p = 0.001), 
      lysine (p = 0.025), and cysteine (p = 0.020), but not histidine. The peptide with 
      the highest sensitivity was cysteine (80.8%) whereas histidine was the least 
      sensitive (11.5%). The data presented show that measuring peptide reactivity has 
      utility for screening chemicals for their skin sensitization potency and thus 
      potential for reducing our reliance on animal test methods.
FAU - Gerberick, G Frank
AU  - Gerberick GF
AD  - Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45253-8707, 
      USA. gerberick.gf@pg.com
FAU - Vassallo, Jeff D
AU  - Vassallo JD
FAU - Bailey, Ruth E
AU  - Bailey RE
FAU - Chaney, Joel G
AU  - Chaney JG
FAU - Morrall, Steve W
AU  - Morrall SW
FAU - Lepoittevin, Jean-Pierre
AU  - Lepoittevin JP
LA  - eng
PT  - Journal Article
DEP - 20040714
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Allergens)
RN  - 0 (Amino Acids)
RN  - 0 (Peptides)
RN  - 4QD397987E (Histidine)
RN  - GAN16C9B8O (Glutathione)
RN  - K3Z4F929H6 (Lysine)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Algorithms
MH  - Allergens/*toxicity
MH  - Amino Acids/chemistry
MH  - Animals
MH  - Calibration
MH  - Chromatography, High Pressure Liquid
MH  - Cysteine/chemistry/toxicity
MH  - Dermatitis, Allergic Contact/*diagnosis
MH  - Female
MH  - Glutathione/metabolism
MH  - Histidine/chemistry/toxicity
MH  - Kinetics
MH  - Local Lymph Node Assay
MH  - Lysine/chemistry/toxicity
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Peptides/chemistry/*toxicity
MH  - Skin Tests
MH  - Spectrophotometry, Ultraviolet
MH  - Structure-Activity Relationship
EDAT- 2004/07/16 05:00
MHDA- 2005/02/05 09:00
CRDT- 2004/07/16 05:00
PHST- 2004/07/16 05:00 [pubmed]
PHST- 2005/02/05 09:00 [medline]
PHST- 2004/07/16 05:00 [entrez]
AID - kfh213 [pii]
AID - 10.1093/toxsci/kfh213 [doi]
PST - ppublish
SO  - Toxicol Sci. 2004 Oct;81(2):332-43. doi: 10.1093/toxsci/kfh213. Epub 2004 Jul 14.