title: Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.
abstract: Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans.
authors.affiliation: Wadsworth Center, New York State Department of Health , Albany, New York 12201, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
authors.affiliation: Wadsworth Center, New York State Department of Health , Albany, New York 12201, United States.
authors.forename: Kerri
authors.initials: K
authors.lastname: Kluetzman
authors.affiliation: Wadsworth Center, New York State Department of Health , Albany, New York 12201, United States.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: College of Nanoscale Science, SUNY Polytechnic Institute , Albany, New York 12203, United States.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D002853:Chromatography, Liquid; D004781:Environmental Exposure; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D002273:Carcinogens; D012333:RNA, Messenger; D012709:Serum Albumin