Functional analysis of N-acetyltransferase (NAT1*14B and NAT1*10) in complete NATb and NATa mRNA.

Content Provider	Semantic Scholar
Author	Millner, Lori Michele
Copyright Year	2011
Abstract	FUNCTIONAL ANALYSIS OF N-ACETYL TRANSFERASE (NAT1 *148 AND NAT1*10) IN COMPLETE NATb AND NATa mRNA Lori Millner August 8, 2011 N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4aminobiphenyl (ASP). NAT1 catalyzes N-acetylation of arylamines as well as the 0acetylation of N-hydroxylated arylamines. O-acetylation leads to the formation of electrophilic intermediates that result in DNA adducts and mutations. NAT1 is transcribed from a major promoter, NATb, and an alternative promoter, NATa, resulting in mRNAs with distinct 5'-untranslated regions (UTR). NATa mRNA is expressed primarily in the kidney, liver, trachea and lung while NATb mRNA has been detected in all tissues studied. To determine if differences in 5'-UTR have functional effect upon NAT1 activity and DNA adducts or mutations following exposure to ASP, pcDNA5/FRT plasmid constructs were prepared for transfection of full length human mRNAs including the 5'-UTR derived from NATa or NATb, the open reading frame, and 888 nucleotides of the 3'-UTR. Following stable transfection of NATb/NAT1*4 or NATa/NAT1*4 into nucleotide excision repair (NER) deficient Chinese hamster ovary cells, Nand 0acetyltransferase activity (in vitro and in situ), mRNA, and protein expression were higher in NATb/NAT1*4 than NATa/NAT1*4 transfected cells (p
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DOI	10.18297/etd/985
Alternate Webpage(s)	http://ir.library.louisville.edu/cgi/viewcontent.cgi?article=1984&context=etd
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Alternate Webpage(s)	https://doi.org/10.18297/etd%2F985
Language	English
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Resource Type	Article