Carcinogenesis

In Vivo Studies

We make use of a modified Ito's liver bioassay to assess the carcinogenic potential of chemicals and chemical mixtures. The results of these experiments is pharmacodynamic information for each chemical of interest; in particular, time-course number, size, and distribution of preneoplastic and neoplastic foci in the liver as a function of exposure dose.

Below are serial sections of a possible hepatocellular adenoma in a male F344 rat treated with PCB126 stained with (A) hematoxylin and eosin, (B) glutathione S-transferase, (C) transforming growth factor α, (D) transforming growth factor β type II receptor, (E) bromo-deoxy-uridine:

In addition to in vivo studies, we employ in silico tools like clonal growth modeling to gain insight into carcinogenesis by simulating the actual experiments using different series of biological assumptions.

In Vitro Studies

Similar to the in vivo experimentation described above, we make use of cell culture techniques to explore chemically-induced carcinogenesis. Our group typically uses immortalized human epidermal keratinocytes (RHEK) as a model system for exposure.

Below are microscope photos detailing cell morphology results from an RHEK chemical carcinogenesis study:


control cells	acetone solvent control	benzo[a]pyrene + marine diesel fuel

Like with the in vivo experiments, we employ clonal growth modeling to augment knowledge gained from the cell culture experiments we perform.

Imaging Studies

With Dr. Ted Watson and Rocky Mountain Magnetic Resonance, we are using NMR imaging to gain insight into the process of chemically-induced carcinogenesis. Current studies are aimed at developing a framework that integrates non-invasive imaging with a mathematical modeling methodology to accurately determine microscopic morphology and associated tissue properties that can indicate the presence of cancer.

Image of spatially-resolved physical properties derived from coupling NMR imaging and mathematical modeling:

Representative Group Publications:

Perez, D. S., Fox, M., Yang, R. S. H., and Campain, J. A. (2003). Arsenic and benzo[a]pyrene differentially alter the capacity for differentiation and growth properties of primary human epidermal keratinocytes. Toxicol. Sci. 76: 280-290.
Bae, D., Handa, R. J., Yang, R. S. H., and Campain, J. A. (2003). Gene expression patterns as potential molecular biomarkers for malignant cellular transformation in human keratinocytes treated with MNNG, arsenic, or metal mixture. Toxicol. Sci. 74:32-42.
Ou, Y.C., Connolly, R.B., Thomas, R.S., Gustafson, D. L., Long, M. E., Dobrev, I., Chubb, L., Xu, Y., Lapidot, S. A., Andersen, M.E., and Yang, R.S.H. (2003). Stochastic simulations of hepatic preneoplastic foci development for four chlorobenzene congeners in a medium-term bioassay. Toxicol. Sci. 73:301-314.
Bae, D. S., Hanneman, W. H., Yang, R. S. H., and Campain, J. A. (2002). Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: Application of cDNA microarray technology. Environ. Health Perspect. 110 (Supplement 6):931-941.