Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Hein, David W.
Toxicology--Animal models; Pharmacology, Experimental
This thesis begins by reviewing human N-acetyltransferases (Chapter I), then outlines experiments involving human hepatocytes and rat N-acetyltransferases (Chapters II-V). These experiments facilitated the development of a dissertation project designed to study N-acetyltransferase tissue-specific expression in inbred rat strains (Chapter VI). Real-time PCR experiments concluded that genetic and/or environmental factors influence N-acetyltransferase expression in cryopreserved human hepatocytes. Therefore, an animal model must be used to study N-acetyltransferase expression. Initial studies of recombinanatly expressed rat N-acetyltransferases (Nats) revealed a correlation between rat and human N-acetyltransferases in nucleotide and amino acide sequence, catalytic activity, substrate selectivity and thermostability, suggesting the rat is an acceptable model for such studies. Disseration aims outlined for studying rat N-acetyltransferase expression in tissues of various inbred rat strains involve analysis of tissue-specific mRNA splicing, mRNA expression, protein expression, and enzyme activity, and a study of cigarette smoke inhalation as a possible environmental influence on Nat expression.
Walraven, Jason Matthew, "Investigations of N-acetyltransferases in human hepatocytes and rat models." (2005). Electronic Theses and Dissertations. Paper 1504.