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Asbestos induces activator protein-1 transactivation in transgenic mice.

Ding-M; Dong-Z; Chen-F; Pack-D; Ma-W; Ye-J; Shi-X; Castranova-V; Vallyathan-V

Cancer Res 1999 Apr; 59(8):1884-1889

http://cancerres.aacrjournals.org/content/59/8/1884

20000967

Activation of activator protein (AP-1) by crocidolite asbestos was examined in vitro in a JB6 P+ cell line stably transfected with AP-1-luciferase reporter plasmid and in vivo using AP-1-luciferase reporter transgenic mice. In in vitro studies, crocidolite asbestos caused a dose- and time-dependent induction of AP-1 activation in cultured JB6 cells. The elevated AP-1 activity persisted for at least 48 h. Crocidolite asbestos also induced AP-1 transactivation in the pulmonary and bronchial tissues of transgenic mice. AP-1 activation was observed at 2 days after intratracheal instillation of the mice with asbestos. At 3 days postexposure, AP-1 activation was elevated 10-fold in the lung tissue and 22-fold in bronchiolar tissue as compared with their controls. The induction of AP-1 activity by asbestos appeared to be mediated through the activation of mitogen-activated protein kinase family members, including extracellular signal-regulating protein kinase, 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 in bronchiolar tissue. The data suggest that further investigation of the role of AP-1 activation in asbestos-induced cell proliferation and carcinogenesis is warranted. In addition, investigation of the potential therapeutic benefits of aspirin in the prevention/amelioration of asbestos-induced cancer is justified.

Pulmonary-cancer; Carcinomas; In-vitro-studies; In-vivo-studies; Mesothelial-cells; Animal-studies; Bronchial-cancer; Pulmonary-system-disorders

CNREA8

12201-28-4

19990415

Journal Article

1999

8

0008-5472

HELD

Cancer Research

WV; MN