Experimental Study On Oxidative Stress Induced By Extracts Of Gasoline Engine Exhaust In Vivo And In Vitro

Gasoline engine exhaust, which contains identified or suspicious carcinogen, has become the main source of outdoor air pollution in most cities. Literatures show that the exposure of Gasoline engine exhaust has the relationship with morbidity of pulmonary and extra-pulmonary diseases increasing.Gasoline engine exhaust had been definited 2B carcinogen by International Agency for Research on Cancer (IARC) in 1989, but so far, it's difficult to reach the consensus in correlation between Gasoline engine exhaust exposure and lung cancer depending on the evidences form epidemiology, animal experiment and toxicity mechanism.We aim to study the correlation between Gasoline engine exhaust exposure and lung cancer, have a further study about the Gasoline engine exhaust toxicity effective and reveal the role of oxidative damage in Gasoline engine exhaust toxicity mechanism.In present study, A549 cells were treated with organic extracts of condensate, condensate, particulate and semivolatile organic compounds from Gasoline engine exhaust. Then the changes of cell survival rate, contents of reactive oxygen species (ROS) and malonaldehyde (MDA) as well as carbonyl protein, activities of antioxidase, DNA single strand break and chromosome damage were determinded. Meanwhile, in order to further understand the relation of toxicity of Gasoline engine exhaust and oxidative damage, A549 cells were treated with glutathione (GSH) for 2 hours firstly. Then these cells were exposure to Gasoline engine exhaust and the same parameters above were observed. The results showed that gasoline could decrease cells survival, increase contents of ROS, induced lipid, protein, DNA and chromosome damage. On the other hand, GSH could inliibit these damages induced by gasoline. Taking together, these data indicated that oxidative stress may be one of Gasoline engine exhaust toxic mechanisms.Considered the characteristic of chemical components from Gasoline engine exhaust and limitations of test in vitro, according to EPA's regulation on assessment of new fuels, the extracts of condensate, particulate and semivolatile organic compounds were administered to Sprague-Dawley rats by intratracheal instillation at the dose of 5.6,16.7 and 50.0 L/ml once a week for 4 weeks. Then, the effects on rat lung, brain, liver and testicle were determined. Our results showed that the extracts of Gasoline engine exhaust could induce lipid peroxidation, oxidative protein damage; DNA single strand break and activity change of the antioxidase, promote inflammation of the lung and increase contents of 8-oxoguanine DNA glycosylase-l(OGGl) of rat lung. In addition, obivious pathological changes in type I, II alveolar and respiratory bronchiole epithelium cells of lungs, including vacuolation of osmiophilic multilamellar bodies . decrease in the number of microvillus, mitochondrial pyknosis or swelling and various changes of nucleus and chromatin, were observed. At the same time, increase of contents of MDA, carbonyl protein (CP) and rate of tailed cells, decrease of activities of superoixde dismutase (SOD) and glutathione peroxidase (GPx) were found in rat brain, liver and testicles after exposure to gasoline exhause. These results resulting from different organs indicated suggested that the damage induced by Gasoline engine exhaust was multi-organ, and oxidative damage maybe play an important role in mechanism of toxic action.In summary, all results both in vivo and in vitro showed that Gasoline engine exhaust could induce dose-dependent oxidative lipid, nucleic acid and protein damage in multi-organ as well as change of contents of DNA repair enzyme. Those damages and changes maybe increased possibility of malignant tumour initiation, promotion and progression.