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Participation of MAP kinase p38 and IkB kinase in chromium (VI)-induced NF-kB and AP-1 activation.

Chen-F; Ding-M; Lu-Y; Leonard-SS; Vallyathan-V; Castranova-V; Shi-X

J Environ Pathol Toxicol Oncol 2000 Jul-Sep; 19(3):231-238

http://www.begellhouse.com/journals/0ff459a57a4c08d0.html

20020639

Epidemiological studies demonstrate that environmental and occupational exposure of chromium(VI) [Cr(VI)] or Cr(VI)-containing particles can cause a number of human diseases, including inflammation and cancer. The biological mechanisms responsible for the initiation and progression of diseases resulting from exposure to Cr(VI) are not fully understood. The present studies evaluated the ability of Cr(IV) to induce activation of NF-kappaB and AP-1, two important transcription factors governing the expression of many early response genes involved in inflammation and carcinogenesis. The activation of NF-kappaB and AP-1 by Cr(IV) was dose dependent. Aspirin, a well-established antioxidant, substantially inhibited Cr(VI)-induced activation of both NF-kappaB and AP-1. SB202190, a specific inhibitor for p38, attenuated AP-1 activation induced by Cr(IV), whereas PD98059, a specific inhibitor for Erk, exhibited no effect on Cr(IV)-induced AP-1 activation. Blockage of NF-kappaB signaling pathway by a transient transfection of a dominant negative expressing vector for IkappaB kinase beta resulted in inhibition of Cr(IV)-induced NF-kappaB, but not AP-1 activation. These data suggest that the activation of AP-1 or NF-kappaB by Cr(IV) is through the involvement of MAP kinase or IKK pathway, respectively.

Chromium-compounds; Epidemiology; Occupational-exposure; Diseases; Cancer; Biological-factors; Genes; Carcinogenesis; Carcinogenicity; Carcinogens; Antioxidants

The Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505

JEPOEC

7440-47-3

20000701

Journal Article

lfd3@cdc.gov

2000

3

0731-8898

HELD

Journal of Environmental Pathology, Toxicology, and Oncology

WV