PMID- 15025500
OWN - NLM
STAT- MEDLINE
DCOM- 20041008
LR  - 20210702
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 17
IP  - 3
DP  - 2004 Mar
TI  - Protein binding and metabolism influence the relative skin sensitization 
      potential of cinnamic compounds.
PG  - 301-10
AB  - Skin protein modification (haptenation) is thought to be a key step in the 
      manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For 
      sensitizing chemicals that are not protein reactive, it is hypothesised that 
      metabolic activation can convert such chemicals into protein reactive toxins 
      within the skin. trans-Cinnamaldehyde, alpha-amyl cinnamaldehyde, and 
      trans-cinnamic alcohol are known sensitizers with differing potencies in man, 
      where the former two are protein reactive and the latter is not. Here, we have 
      used immunochemical methods to investigate the extent of protein-cinnamaldehyde 
      binding in rat and human skin homogenates that have been incubated (for either 5, 
      15, 30, or 60 min) at 37 degrees C with cinnamaldehyde, alpha-amyl cinnamaldehyde 
      (at concentrations of between 1 and 40 mM), and cinnamic alcohol (at higher 
      concentrations of 200 or 400 mM). Cinnamaldehyde specific antiserum was raised 
      specially. A broad range (in terms of molecular mass) of protein-cinnamaldehyde 
      adducts was detected (as formed in a time- and concentration-dependent manner) in 
      skin treated with cinnamaldehyde and cinnamic alcohol but not with alpha-amyl 
      cinnamaldehyde. Mechanistic observations have been related to relative skin 
      sensitization potential, as determined using the local lymph node assay (LLNA) as 
      a biological read-out. The work presented here suggests that there is a common 
      hapten involved in cinnamaldehyde and cinnamic alcohol sensitization and that 
      metabolic activation (to cinnamaldehyde) is involved in the latter. Conversely, 
      there does not appear to be a common hapten for cinnamaldehyde and alpha-amyl 
      cinnamaldehyde. Such mechanistic work on protein modification is important in 
      understanding the early mechanisms of skin sensitization. Such knowledge can then 
      be used in order that effective and appropriate in vitro/in silico tools for 
      predicting sensitization potential, with a high confidence, can be developed.
FAU - Elahi, Eiram N
AU  - Elahi EN
AD  - Biological Chemistry Section, Division of Biomedical Sciences, Imperial College 
      School of Medicine, Sir Alexander Fleming Building, South Kensington, London, 
      United Kingdom, SW7 2AZ.
FAU - Wright, Zoe
AU  - Wright Z
FAU - Hinselwood, David
AU  - Hinselwood D
FAU - Hotchkiss, Sharon A M
AU  - Hotchkiss SA
FAU - Basketter, David A
AU  - Basketter DA
FAU - Pease, Camilla K Smith
AU  - Pease CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Aldehydes)
RN  - 0 (Propanols)
RN  - 122-40-7 (2-pentylcinnamaldehyde)
RN  - 7864XYD3JJ (Acrolein)
RN  - SR60A3XG0F (cinnamaldehyde)
RN  - SS8YOP444F (cinnamyl alcohol)
SB  - IM
MH  - Acrolein/*analogs & derivatives/*pharmacokinetics/toxicity
MH  - Aldehydes/pharmacokinetics/toxicity
MH  - Animals
MH  - Dermatitis, Contact/etiology/*metabolism/pathology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Local Lymph Node Assay
MH  - Propanols/pharmacokinetics/toxicity
MH  - Protein Binding
MH  - Rabbits
MH  - Rats
MH  - Rats, Inbred F344
MH  - Skin/drug effects/*metabolism/pathology
EDAT- 2004/03/18 05:00
MHDA- 2004/10/09 09:00
CRDT- 2004/03/18 05:00
PHST- 2004/03/18 05:00 [pubmed]
PHST- 2004/10/09 09:00 [medline]
PHST- 2004/03/18 05:00 [entrez]
AID - 10.1021/tx0341456 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2004 Mar;17(3):301-10. doi: 10.1021/tx0341456.