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Related Experiment Videos

Aflatoxin B1 activation in human lung

J D Kelly1, D L Eaton, F P Guengerich

  • 1Program in Toxicology and Molecular Biology, Utah State University, Logan 84322-4620, USA.

Toxicology and Applied Pharmacology
|May 1, 1997
PubMed
Summary
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Occupational inhalation of aflatoxin B1 (AFB1) may cause lung cancer. Human lung microsomes activate AFB1 to a carcinogenic epoxide, with cytochrome P450 3A (CYP3A) likely responsible.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Occupational Health

Background:

  • Inhalation exposure to aflatoxin B1 (AFB1), a carcinogen, is a concern in certain occupations.
  • Epidemiological data suggest a link between AFB1 inhalation and primary lung cancer.

Purpose of the Study:

  • To investigate the activation of AFB1 by human lung microsomes.
  • To identify the specific cytochrome P450 (CYP) enzymes involved in AFB1 activation in the lung.

Main Methods:

  • Human lung microsomes were incubated with [3H]AFB1.
  • AFB1 activation was measured by quantifying the AFB1-glutathione (AFB1-GSH) conjugate using HPLC.
  • The role of CYP3A was assessed using nifedipine oxidation, immunoinhibition with anti-CYP3A4 IgG, and immunoblot analysis.

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Main Results:

  • Human lung microsomes activated AFB1 to the AFB1-8,9-epoxide, measured as AFB1-GSH conjugate formation.
  • CYP3A4 significantly inhibited AFB1 activation, indicating its involvement.
  • AFB1 activation in lung microsomes was lower than in liver, potentially due to fewer CYP-containing cells.

Conclusions:

  • Human lung microsomes activate AFB1 to a potentially carcinogenic epoxide.
  • CYP enzymes of the 3A subfamily are likely responsible for this lung-specific AFB1 activation.
  • In situ AFB1 activation poses a carcinogenic risk in occupational settings with AFB1-contaminated dust inhalation.