Effects of low concentrations of benzene on human lung cells in vitro.
Exposure to benzene causes health hazards to humans. The airway epithelium is a physical barrier to inhaled toxicants and particulates. This is an in vitro basic science study to evaluate the effects of benzene on lung cells without the inflammatory responses triggered by inhalation. Dose-response cytotoxicity was assessed using two cell lines: alveolar derived (A549) human epithelial adenocarcinoma and human lung (LL24) fibroblast. A549 cells were more resistant than LL24 fibroblast lung cells to benzene. LL24 cells demonstrated enhanced proliferation with diluted benzene solutions. Moreover, low concentrations of benzene enhanced telomerase activity in LL24 cells while no effects were observed in the adenocarcinoma cells. Proteolysis of lung matrix by matrix metalloproteinases (MMPs) is an early event observed in lung pathologies. Benzene increased MMP-2 and MMP-3 mRNA. Using the ratio (MMP-1+MMP-2+MMP-3)/(TIMP-1+TIMP-2), as an index of prodestructive activity, we observed a dose-dependent increase. The overall higher expression levels of MMPs in benzene treated cells did not appear to be controlled by TIMPs, which are negatively correlated. Comparing different cell lines, we demonstrated how crucial is the target's susceptibility. Our observations may represent early functional alterations that occur in the airways of exposed people.
Giuliano
Mariateresa
M
Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Medical School, II University of Naples, Via L. De Crecchio 7, Naples, Italy. mariateresa.giuliano@unina2.it
Stellavato
Antonietta
A
Cammarota
Marcella
M
Lamberti
Monica
M
Miraglia
Nadia
N
Sannolo
Nicola
N
De Rosa
Mario
M
D001554:Benzene / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D045726:Metalloproteases / Q000096:biosynthesis; D019098:Telomerase / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019098:Telomerase; D045726:Metalloproteases; D001554:Benzene