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.
Polymorphism of Quinone-metabolizing enzymes and susceptibility to ozone-reduced acute effects
BERGAMASCHI, Enrico;
2001-01-01
Abstract
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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