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

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO 1) and glutathione-S-transferase mu -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 sampl e for the measurement of the Clara cell protein CC16. NQO1 and GSTM71 polym orphisms were characterized by polymerase chain reaction-based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of pe ripheral leukocytes. Rides at O-3 > 80 ppb resulted in significant decremen ts of pulmonary function tests and increased levels of serum CC16, consiste nt with mild impairment in respiratory function and increased lung epitheli al 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 cl osely associated with each other and with O-3 levels, whereas no such relat ionships were found among subjects bearing other haplotypes. An increased r eaction rate between O-3 and hydroquinones would be consistent with the gre ater increase in 8-OHdG after O-3 exposure in this "susceptible" group.