Gene expression changes in rat brain after short and long exposures to particulate matter in Los Angeles basin air: Comparison with human brain tumors.
Air pollution negatively impacts pulmonary, cardiovascular, and central nervous systems. Although its influence on brain cancer is unclear, toxic pollutants can cause blood-brain barrier disruption, enabling them to reach the brain and cause alterations leading to tumor development. By gene microarray analysis validated by quantitative RT-PCR and immunostaining we examined whether rat (n=104) inhalation exposure to air pollution particulate matter (PM) resulted in brain molecular changes similar to those associated with human brain tumors. Global brain gene expression was analyzed after exposure to PM (coarse, 2.5-10μm; fine, <2.5μm; or ultrafine, <0.15μm) and purified air for different times, short (0.5, 1, and 3 months) and chronic (10 months), for 5h per day, four days per week. Expression of select gene products was also studied in human brain (n=7) and in tumors (n=83). Arc/Arg3.1 and Rac1 genes, and their protein products were selected for further examination. Arc was elevated upon two-week to three-month exposure to coarse PM and declined after 10-month exposure. Rac1 was significantly elevated upon 10-month coarse PM exposure. On human brain tumor sections, Arc was expressed in benign meningiomas and low-grade gliomas but was much lower in high-grade tumors. Conversely, Rac1 was elevated in high-grade vs. low-grade gliomas. Arc is thus associated with early brain changes and low-grade tumors, whereas Rac1 is associated with long-term PM exposure and highly aggressive tumors. In summary, exposure to air PM leads to distinct changes in rodent brain gene expression similar to those observed in human brain tumors.
['Ljubimova|Julia Y|JY|', 'Kleinman|Michael T|MT|', 'Karabalin|Natalya M|NM|', 'Inoue|Satoshi|S|', 'Konda|Bindu|B|', 'Gangalum|Pallavi|P|', 'Markman|Janet L|JL|', 'Ljubimov|Alexander V|AV|', 'Black|Keith L|KL|']
D000397:Air Pollution D000818:Animals D001932:Brain Neoplasms D003598:Cytoskeletal Proteins D005786:Gene Expression Regulation D006801:Humans D007150:Immunohistochemistry D015141:Los Angeles D008297:Male D009419:Nerve Tissue Proteins D020411:Oligonucleotide Array Sequence Analysis D052638:Particulate Matter D051381:Rats D011916:Rats, Inbred F344 D060888:Real-Time Polymerase Chain Reaction D059467:Transcriptome D020830:rac1 GTP-Binding Protein
Brain tumor Gene microarray Arc/Arg3.1 Rac1 Air pollution particles Chronic exposure