Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects

Am J Respir Crit Care Med. 2001 May;163(6):1426-31. doi: 10.1164/ajrccm.163.6.2006056.


The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Acute Disease
  • Adult
  • Air Pollutants / adverse effects*
  • Benzoquinones / metabolism*
  • Bronchial Hyperreactivity / chemically induced*
  • Bronchial Hyperreactivity / diagnosis
  • Bronchial Hyperreactivity / genetics*
  • Bronchial Hyperreactivity / metabolism
  • Deoxyguanosine / analogs & derivatives*
  • Environmental Exposure / adverse effects*
  • Female
  • Gene Frequency
  • Genotype
  • Glutathione Transferase / genetics*
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Oxidants, Photochemical / adverse effects*
  • Ozone / adverse effects*
  • Polymerase Chain Reaction
  • Proteins
  • Uteroglobin*


  • Air Pollutants
  • Benzoquinones
  • Oxidants, Photochemical
  • Proteins
  • SCGB1A1 protein, human
  • quinone
  • Ozone
  • 8-Hydroxy-2'-Deoxyguanosine
  • Uteroglobin
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Deoxyguanosine