Date of Graduation


Document Type


Degree Type



School of Medicine


Microbiology, Immunology, and Cell Biology

Committee Chair

Xianglin Shi.


Low dose chronic exposure to environmental carcinogens is a major cause of human cancers. More than 375 known or suspected environmental carcinogens have been identified, many of which are transition metals or metal containing compounds (IARC, updated to 2004, Although much research has focused on the ability of these metals to induce reactive oxygen species formation (ROS), DNA damage, and apoptosis, less effort has been put forth to examine the cellular signaling mechanisms responsible for these effects. Our experimental research has focused on the signaling pathways induced in response to arsenic exposure. Arsenic is a highly interesting transition metal due to its widespread exposure and paradoxic ability to induce carcinogenesis as well as apoptosis. Here, we highlight the importance of the human genome project in advancing the knowledge of the molecular mechanisms of metal-induced toxicology/carcinogenesis. In addition, we review the latest research in the field of metal-induced carcinogenesis. Finally, we describe a mechanism for the induction of the growth-arrest and DNA damage inducible protein 45 alpha (GADD45alpha) involving arsenic-induced ROS formation in the non-tumorigenic human lung airway epithelial cell line, BEAS-2B.