Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Discrimination of haptens from prohaptens using the metabolically deficient Cpr(low/low) mouse.

Authors
Chipinda-I; Blachere-FM; Anderson-SE; Siegel-PD
Source
Toxicol Appl Pharmacol 2011 May; 252(3):268-272
NIOSHTIC No.
20038769
Abstract
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.
Keywords
Allergic-disorders; Allergic-reactions; Allergies; Biological-effects; Cell-biology; Cellular-reactions; Chemical-hypersensitivity; Laboratory-animals; Physical-reactions; Dermatitis; Contact-dermatitis; Contact-allergies; Physiological-measurements; Physiological-response; Skin-exposure; Skin-irritants; Author Keywords: Skin sensitizers; Hapten; Prohapten; Cutaneous metabolism
Contact
Itai Chipinda, Allergy & Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
TXAPA9
Publication Date
20110501
Document Type
Journal Article
Email Address
IChipinda@cdc.gov
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0041-008X
NIOSH Division
HELD
Priority Area
Services
Source Name
Toxicology and Applied Pharmacology
State
WV
TOP