Medicine and Health Sciences Commons^™

Dna-Protein Cross-Linking By Pyrrolizidine Alkaloids, Gail L. Drew

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Pyrrolizidine alkaloids (PAs) are natural plant compounds found in hundreds of plant species worldwide and are reported to have cytotoxic, carcinogenic, antimitotic, and genotoxic activity. PAs are metabolized by the cytochrome P450 (CYP) system to the pyrrole or the N-oxide form. The pyrroles are bifunctional electrophilic alkylators that bind cellular nucleophiles such as DNA and proteins and sirupt normal cell processes, including DNA replication and gene transcription and can cause megalocytosis. The pyrroles dehydrosenecionine (DHSN) and dehydromonocrotaline (DHMO) are among the most potent PA cross-linkers and inducers of megalocytosis. DHSN and DHMO-induced cross-links in cultured normal (MDBK) and neoplastic (MCF7) …

Aflatoxin B1 Metabolism In Mammalian Pulmonary Tissue, J. Michael Eichelberger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ (AFB₁) is a potent dietary hepatocarcinogen and may be a lung carcinogen when inhaled. To study the relative ability of lung and liver to metabolize AFB₁, a susceptible (Swiss-Webster rat) and resistant species (Syrian golden hamster) were pretreated with inducing agents in order to identify specific AFB₁ metabolizing enzymes in each tissue.

Analysis of AFB₁-exo-epoxide (AFBO) formation, O-dealkynation assays, and protein immunoblots demonstrated that cytochrome P450 (CYP) 1A proteins were overexpressed in both the lung and liver of hamsters pretreated with 3-methylchyolanthrene (3-MC). Only CYP1A1 was expressed in the lung …