Role of Mouse Cytochrome P450 Enzymes of the Cyp2abfgs Subfamilies in the Induction of Lung Inflammation by Cigarette Smoke Exposure

Matthew Hartog, Qing Yu Zhang, Xinxin Ding

Research output: Contribution to journalArticlepeer-review


Many constituents of tobacco smoke (TS) require bioactivation to exert toxic effects; however, few studies have examined the role of bioactivation enzymes in the adverse effects of TS exposure. This knowledge gap is a major source of uncertainty for risk assessment and chemoprevention efforts. Our aim is to test the hypothesis that cytochrome P450 (P450) enzyme-mediated bioactivation is essential to the development of TS exposure-induced lung toxicity, by determining the contributions of P450 enzymes in the mouse Cyp2abfgs gene subfamilies to environmental tobacco smoke (ETS)-induced lung inflammation. Adult female wildtype (WT) and Cyp2abfgs-null mice (both on C57BL/6J background) were exposed to filtered air or ETS, intermittently, for 1 or 2 weeks. Lung inflammation was assessed by quantification of inflammatory cells, cytokines, chemokines, and proteins in bronchoalveolar lavage fluid (BALF) and histopathological analysis. Glutathione (GSH) conjugates of 2 ETS constituents, naphthalene (NA), and 3-methylindole (3MI), were measured in mice exposed to ETS for 4 h. Persistent macrophagic and neutrophilic lung inflammation was observed in ETS-exposed WT mice; the extent of which was significantly reduced in ETS-exposed Cyp2abfgs-null mice. Levels of proinflammatory cytokines and chemokines, along with the total protein concentration, were increased in cell-free BALF from ETS-exposed WT mice, but not Cyp2abfgs-null mice. Additionally, GSH conjugates of NA and 3MI were detected in the lungs of WT, but not Cyp2abfgs-null, mice following ETS exposure. These results provide the first in vivo evidence that the mouse Cyp2abfgs gene cluster plays an important role in ETS-induced lung inflammation.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalToxicological Sciences
Issue number1
StatePublished - Nov 1 2019


  • 3-methylindole
  • cytochrome P450
  • glutathione conjugates
  • lung toxicity
  • naphthalene
  • tobacco smoke

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Role of Mouse Cytochrome P450 Enzymes of the Cyp2abfgs Subfamilies in the Induction of Lung Inflammation by Cigarette Smoke Exposure'. Together they form a unique fingerprint.

Cite this