Back to Search
Start Over
Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice.
- Source :
-
Environmental Health Perspectives . Jun2017, Vol. 125 Issue 6, p1-10. 10p. 2 Diagrams, 2 Charts, 2 Graphs. - Publication Year :
- 2017
-
Abstract
- BACKGROUND: The potential carcinogenicity of naphthalene (NA), a ubiquitous environmental pollutant, in human respiratory tract is a subject of intense debate. Chief among the uncertainties in risk assessment for NA is whether human lung CYP2A13 and CYP2F1 can mediate NA's respiratory tract toxicity. OBJECTIVES: We aimed to assess the in vivo function of CYP2A13 and CYP2F1 in NA bioactivation and NA-induced respiratory tract toxicity in mouse models. METHODS: Rates of microsomal NA bioactivation and the effects of an anti-CYP2A antibody were determined for lung and nasal olfactory mucosa (OM) from Cyp2abfgs-null, CYP2A13-humanized, and CYP2A13/2F1-humanized mice. The extent of NA respiratory toxicity was compared among wild-type, Cyp2abfgs-null, and CYP2A13/2F1-humanized mice following inhalation exposure at an occupationally relevant dose (10 ppm for 4 hr). RESULTS: In vitro studies indicated that the NA bioactivation activities in OM and lung of the CYP2A13/2F1-humanized mice were primarily contributed by, respectively, CYP2A13 and CYP2F1. CYP2A13/2F1-humanized mice showed greater sensitivity to NA than Cyp2abfgs-null mice, with greater depletion of nonprotein sulfhydryl and occurrence of cytotoxicity (observable by routine histology) in the OM, at 2 or 20 hr after termination of NA exposure, in humanized mice. Focal, rather than gross, lung toxicity was observed in Cyp2abfgs-null and CYP2A13/2F1-humanized mice; however, the extent of NA-induced lung injury (shown as volume fraction of damaged cells) was significantly greater in the terminal bronchioles of CYP2A13/2F1-humanized mice than in Cyp2abfgs-null mice. CONCLUSION: CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HYDROCARBON metabolism
*HYDROCARBON analysis
*ANIMAL experimentation
*BIOLOGICAL assay
*BIOLOGICAL models
*GENETIC techniques
*HYDROCARBONS
*IMMUNOGLOBULINS
*LUNGS
*MICE
*MICROSCOPY
*NASAL mucosa
*PROBABILITY theory
*RESEARCH funding
*STAINS & staining (Microscopy)
*STATISTICS
*TOXICITY testing
*DATA analysis
*INHALATION injuries
*DESCRIPTIVE statistics
*IN vitro studies
*ONE-way analysis of variance
*IN vivo studies
*CYTOCHROME P-450
*PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 00916765
- Volume :
- 125
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Environmental Health Perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 124228385
- Full Text :
- https://doi.org/10.1289/EHP844