PMID- 21376747
OWN - NLM
STAT- MEDLINE
DCOM- 20110711
LR  - 20141120
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 252
IP  - 3
DP  - 2011 May 1
TI  - Discrimination of haptens from prohaptens using the metabolically deficient 
      Cpr(low/low) mouse.
PG  - 268-72
LID - 10.1016/j.taap.2011.02.018 [doi]
AB  - The murine local lymph node assay (LLNA) is a validated, well accepted method for 
      identification of chemical contact allergens. Both direct acting haptens and 
      prohaptens (requiring metabolic activation) can be identified, but not 
      differentiated by this assay. This study was used to assess the utility of a pan 
      microsomal metabolic deficient mouse to distinguish between direct acting haptens 
      and prohaptens in the LLNA. Hapten and prohapten induced cell proliferation was 
      compared in C57BL/6J (B6) wild type (WT) versus homozygous (HO) knockout mice 
      with a hypomorphic NADPH-Cytochrome P450 Reductase (CPR) gene (termed 
      Cpr(low/low)) resulting in low CPR enzyme activity. Mice were dosed with known 
      prohaptens; benzo(a)pyrene (BaP), carvone oxime (COx) and paracetamol (PCM) and 
      haptens; oxazolone (OX), 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (EtOX), and 
      N-acetylbenzoquinoneimine (NABQI) in this study. Skin microsomes from the WT, HO 
      and heterozygous (HT) Cpr(low/low) mice were compared and evaluated for CPR 
      activity. Lymphocyte proliferative responses to BaP, COx and PCM were 
      significantly abrogated by 36.4%, 45.2% and 50.8%, respectively; in Cpr(low/low) 
      knock out (KO) mice versus WT mice; while the lymphocyte proliferative responses 
      to the direct acting haptens OX, EtOX and NABQI were comparable. CPR activity, 
      determined as Units/mg protein, was determined to be significantly lower in the 
      Cpr(low/low) mice compared to the WT. Results of the present study suggest 
      potential utility of the Cpr(low/low) mice in the LLNA to differentiate 
      prohaptens from direct acting haptens.
CI  - Published by Elsevier Inc.
FAU - Chipinda, Itai
AU  - Chipinda I
AD  - Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, 
      National Institute for Occupational Safety and Health, 1095 Willowdale Road, 
      Morgantown,WV 26505-2888, USA. IChipinda@cdc.gov
FAU - Blachere, Francoise M
AU  - Blachere FM
FAU - Anderson, Stacey E
AU  - Anderson SE
FAU - Siegel, Paul D
AU  - Siegel PD
LA  - eng
PT  - Journal Article
DEP - 20110303
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Allergens)
RN  - 0 (Haptens)
RN  - EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase)
SB  - IM
MH  - Allergens/metabolism/*pharmacology
MH  - Animals
MH  - Female
MH  - Haptens/metabolism/*pharmacology
MH  - In Vitro Techniques
MH  - Local Lymph Node Assay
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NADPH-Ferrihemoprotein Reductase/deficiency/genetics/*metabolism
MH  - Skin/*drug effects/metabolism
EDAT- 2011/03/08 06:00
MHDA- 2011/07/12 06:00
CRDT- 2011/03/08 06:00
PHST- 2011/01/04 00:00 [received]
PHST- 2011/02/16 00:00 [revised]
PHST- 2011/02/23 00:00 [accepted]
PHST- 2011/03/08 06:00 [entrez]
PHST- 2011/03/08 06:00 [pubmed]
PHST- 2011/07/12 06:00 [medline]
AID - S0041-008X(11)00072-X [pii]
AID - 10.1016/j.taap.2011.02.018 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2011 May 1;252(3):268-72. doi: 
      10.1016/j.taap.2011.02.018. Epub 2011 Mar 3.