Asbestos induces AP-1 activation in cell culture and transgenic mice.
Ding-M; Dong-ZG; Chen-F; Pack-D; Ma-VY; Ye-JP; Shi-XL; Castranova-V; Vallyathan-V
Carcinogenesis 1999 Mar; 40(8):351
Occupational exposure to asbestos is linked to increased incidence of lung cancer. To investigate the carcinogenic mechanism of asbestos, activation of activator protein (AP-1) by crocidolite asbestos was examined in both a stable AP-1-luciferase reporter plasmid-transfected JB6 p+ cell line and AP-1-luciferase reporter transgenic mice. In the cultured cells asbestos caused a dose-dependent induction of AP-1 activation. The elevated AP-1 activity persisted at least for 48 hours. Asbestos also induced AP-1 transactivation in transgenic mice. AP-1 activation was observed at 2 days after exposure of the mice to asbestos via intratracheal instillation. At 3 days post-exposure, the AP-1 was elevated 10-fold in the lung tissue and 22-fold in bronchial tissue as compared to their controls. This finding is consistent with previous reports showing that asbestos causes site specific bronchogenic carcinoma. The induction effect of asbestos-induced AP-1 activity appeared to be mediated through the activation of MAP kinase family members, including extracellular signal-regulated protein kinases, Erk1 and Erk2. Aspirin inhibited asbestos-induced AP-1 activity in JB6 cells. Pretreatment of the mice with aspirin also inhibited asbestos-induced AP-1 activation. The data suggest that further investigation of the involvement of AP-1 in asbestos-induced cell proliferation and carcinogenesis as well as the potential therapeutic/preventative actions of aspirin in asbestos-induced carcinogenesis is warranted.
Analytical-processes; Analytical-methods; Animal-studies; Animals; Laboratory-animals; Carcinogens; Carcinogenicity; Carcinogenesis; Toxins; Toxic-effects; Cancer; Antioxidants; Exposure-assessment; Statistical-analysis; Respiratory-system-disorders; Pulmonary-system-disorders; Cell-cultures; Cell-damage; Cell-function; Cellular-function; Cellular-reactions; Asbestos-dust; Asbestos-fibers; Asbestos-products