Lisa Peterson, Ph.D.
Graduate Faculty, Department of Medicinal Chemistry
Associate Professor, Environmental and Occupational Health

Research Interests:

My research focuses on genotoxic and nongenotoxic mechanisms by which chemicals initiate cancer. The projects apply organic, biological and analytical chemical methods to this problem. I am particularly interested in studying the events beyond DNA alkylation that contribute to the carcinogenic properties of chemicals.

We have been exploring the mechanisms by which nitrosamines exert their tissue-specific carcinogenic effects. These studies indicate that DNA repair plays a critical role in the overall activity of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) as a lung specific carcinogen. Repair of NNK-derived O⁶-alkylguanine adducts by O⁶-alkylguanine DNA-alkyltransferase (AGT) significantly protects against the mutagenic activity of NNK derived metabolites. We have been exploring how various NNK metabolites affect AGT mediated repair. In addition, we have been characterizing all repair pathways involved in the repair of large O⁶?alkylguanine adducts derived from tobacco-specific nitrosamines. These studies have been extended to investigating the biochemical differences between known human variants of DNA repair proteins in order to understand differences in human susceptibility to cancers associated with tobacco products.

We are also exploring the mechanism by which furan induces liver tumors in laboratory animals.  Furan is the parent compound for a class of chemicals that are toxic or carcinogenic. It is an important industrial intermediate that is also present in the environment. The widespread occurrence of furan and significant potential for human exposure warrant investigation into the toxicological properties of this compound. The specific events involved in tumor induction by this carcinogen are unknown. We have been elucidating the pathways of furan metabolism as well as characterizing the protein and DNA damage resulting from furan exposure. These are important first steps to assessing human health risk from furan exposure.

Publications:

Byrns, M. C., Vu, C. C., Neidigh, J. W., Abad, J. L., Jones, R. A., and Peterson, L. A. (2006) Detection of DNA adducts derived from the reactive metabolite of furan, cis-2-butene-1,4-dial. Chem. Res. Toxicol. 19, 414-420

Mijal, R. S., Kanugula, S., Vu, C. C., Fang, Q., Pegg, A. E., and Peterson, L. A. (2006) DNA sequence context affects repair of the tobacco-specific adduct O⁶-[4-oxo-4-(3-pyridyl)butyl]guanine by human O⁶-alkylguanine-DNA alkyltransferases. Cancer Res. 66, 4968-4974.

Peterson, L. A. (2006) Electrophilic intermediates produced by bioactivation of furan. Drug Metabolism Reviews 38, 615-626.

Peterson, L. A., Cummings, M. E., Chan, J. Y., Vu, C. C., and Matter, B. A. (2006) Identification of a cis-2-butene-1,4-dial-derived glutathione conjugate in the urine of furan-treated rats. Chem Res. Toxicol. 19, 1138-1141.