Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1426-1431

Polymorphism of Quinone-metabolizing Enzymes and Susceptibility to Ozone-induced Acute Effects

ENRICO BERGAMASCHI, GIUSEPPE DE PALMA, PAOLA MOZZONI, SIMONA VANNI, MARIA VITTORIA VETTORI, FABRICE BROECKAERT, ALFRED BERNARD, and ANTONIO MUTTI

Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology, and Health Sciences, University of Parma, Parma, Italy; and Industrial Toxicology and Occupational Medicine Unit, School of Public Health, Faculty of Medicine, Catholic University of Louvain, Brussels, Belgium

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase µ-1 (GSTM1) in the responsiveness to O₃-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O₃ 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 O₃ > 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 O₃ 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 O₃ levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O₃ and hydroquinones would be consistent with the greater increase in 8-OHdG after O₃ exposure in this "susceptible" group.

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