Asbestos fibers persist in the lungs and cause chronic inflammation, pulmonary and pleural fibrosis, lung cancer, and malignant mesothelioma after latent periods of 20-40 years. Recent experimental evidence based on animal models using genetically-engineered mice have provided new insight about the mechanistic links between chronic inflammation, fibrosis, and cancer. Recruitment and activation of inflammatory cells in response to biopersistent fibers is accompanied by release of reactive oxygen species leading to oxidant stress, DNA damage, and mutations. Inflammatory cells can release cytokines and growth factors that stimulate stromal remodeling and angiogenesis. It is hypothesized that reciprocal activation of tumor and stromal cells results in local release of matrix metalloproteinases that facilitate growth and invasion of diffuse malignant mesothelioma. In vitro, ex vivo, and in vivo assays using well-characterized, transplantable murine mesothelial cell lines will be used to test this hypothesis. Newly-developed technologies including laser capture microdissection, cDNA microarrays, and quantitative analysis of gene expression provide powerful tools for this experimental approach.

Kane, Agnes B. Oncogenes and tumor suppressor genes in the carcinogenicity of fibers and particles. Inhalation Toxicology 12: 133-140, 2000.

Vaslet, Charles A., Messier, Norma J., and Kane, Agnes B. Accelerated progression of asbestos-induced mesotheliomas in heterozygous p53 +/- mice. Toxicological Sciences 68: 331-338, 2002.

Professor

M.D., Ph.D. Temple University, 1974, 1976

Brown University
BioMedical Center,
Rm. 511

(401) 863-1110
Agnes_Kane@brown.edu