Date of Completion

Winter 12-15-2019

Thesis Advisor(s)

Ashis K. Basu; Christine Simon

Honors Major

Biological Sciences

Disciplines

Biochemistry, Biophysics, and Structural Biology | Biology | Cell and Developmental Biology | Environmental Chemistry | Organic Chemistry | Organismal Biological Physiology

Abstract

Cancer is a disease that stems from genomic errors that are not corrected properly by cellular repair mechanisms. Errors are more likely to form when organisms are subjected to DNA damage by mutagenic compounds. 1-Nitropyrene, a nitrated polycyclic aromatic hydrocarbon (nitro-PAH), has been shown to be a potent mutagen that causes cancer. Nitro-PAHs can arise from diesel exhaust products in the environment. Out of all nitro-PAHs, 1-nitropyrene is found in largest quantities in the environment. This poses a great need to study its effects biochemically in order to address its toxicity in DNA. Other nitropyrene derivatives, including 1,6-dinitropyrene and 1,8-dinitropyrene, are known to be much more carcinogenic than 1-nitropyrene itself. 1-Nitropyrene reacts with DNA and forms two 2’-deoxyguanosine (dG)-N2adducts: dG-N2-6-aminopyrene and dG-N2-8-aminopyrene. These adducts retain the same conformations as 1,6-dinitropyrene and 1,8-dinitropyrene, respectively. This study assesses each adduct’s toxicity in AB1157 Escherichia coli cells. It was found that dG-N2-6-aminopyrene and dG-N2-8-aminopyrene both have negative effects on bacterial cell viability. However, dG-N2-6-aminopyrene was found to be more toxic than dG-N2-8-aminopyrene.

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