Research Program: Carcinogenesis & Chemoprevention
Professor, Division of Environmental Health Sciences
Graduate Faculty, Department of Medicinal Chemistry

peter431@umn.edu
612-626-0164 — office
612-626-2330 — lab
Preferred method of contact: e-mail

Research Interests

Cancer risk is determined by gene-environment interactions. An individual's risk of developing cancer when exposed to a genotoxic carcinogen depends upon the balance of activation and detoxification metabolic pathways as well as the individual's ability to repair the resulting DNA damage. To perform adequate risk assessment when considering exposure to an environmental chemical, it is important to understand the molecular mechanisms of how the chemical exerts its carcinogenic effects as well as how genetic variations of metabolic and DNA repair proteins influence the cellular response. 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's 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 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. While the specific events involved in tumor induction by this carcinogen are unknown, it is clear that its toxicity requires metabolism to reactive intermediates. We have been elucidating the pathways of furan metabolism as well as exploring the involvement of metabolites in the toxicological properties of furan. These are important first steps to assessing human health risk from furan exposure.

Selected Publications

Mijal, R. S., Loktionova, N. A., Vu, C. C., Pegg, A. E., and Peterson, L. A. O6-Pyridyloxobutylguanine adducts contribute to the mutagenic properties of pyridyloxobutylating agents. Chem Res Toxicol. 2005;18:1619-1625.

Peterson, L. A., Cummings, M. E., Vu, C. C., and Matter, B. A. Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial. Drug Metab Dispos. 2005;33, 1453-1458.

Byrns, M. C., Vu, C. C., Neidigh, J. W., Abad, J. L., Jones, R. A., and Peterson, L. A. Detection of DNA adducts derived from the reactive metabolite of furan, cis-2-butene-1,4-dial. Chem Res Toxicol. 2006;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 O(6)-[4-Oxo-4-(3-pyridyl)butyl]guanine by human O(6)-alkylguanine-DNA alkyltransferases. Cancer Res. 2006;66:4968-4974.