title: Isolevuglandins as a gauge of lipid peroxidation in human tumors.
abstract: The cellular production of free radicals or reactive oxygen species (ROS) can lead to protein, lipid or DNA modifications and tumor formation. The cellular lipids undergo structural changes through the actions of enzymes (e.g. cyclooxygenases) or free radicals to form a class of compounds called Isolevuglandins (IsoLGs). The recruitment and continued exposure of tissue to ROS and IsoLGs causes increased cell proliferation, mutagenesis, loss of normal cell function and angiogenesis. The elevated concentration of ROS in cancerous tissues suggests that these mediators play an important role in cancer development. We hypothesized that tumors with elevated ROS levels would similarly possess an increased concentration of IsoLGs when compared with normal tissue. Using D11, an ScFv recombinant antibody specific for IsoLGs, we utilized immunohistochemistry to visualize the presence of IsoLG in human tumors compared to normal adjacent tissue (NAT) to the same tumor. We found that IsoLG concentrations were elevated in human breast, colon, kidney, liver, lung, pancreatic and tongue tumor cells when compared to NAT and believe that IsoLGs can be used as a gauge indicative of lipid peroxidation in tumors.
authors.affiliation: Department of Radiation Oncology at Washington University in St. Louis, Washington 63110, United States.
authors.forename: H P
authors.initials: HP
authors.lastname: Yan
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: S S
authors.initials: SS
authors.lastname: Davies
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: P
authors.initials: P
authors.lastname: Pohlmann
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: F F
authors.initials: FF
authors.lastname: Parl
authors.affiliation: Biomedical Research Education and Training (BRET), Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: S
authors.initials: S
authors.lastname: Estes
authors.affiliation: Biomedical Research Education and Training (BRET), Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: J
authors.initials: J
authors.lastname: Maeng
authors.affiliation: Biomedical Research Education and Training (BRET), Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: B
authors.initials: B
authors.lastname: Parker
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Biomedical Research Education and Training (BRET), Vanderbilt University School of Medicine, Nashville, TN 37232, United States. Electronic address: r.mernaugh@vanderbilt.edu.
authors.forename: R
authors.initials: R
authors.lastname: Mernaugh
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D010743:Phospholipids / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000906:Antibodies; D005609:Free Radicals; D010743:Phospholipids; D011458:Prostaglandins E; D017382:Reactive Oxygen Species; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Free radicals; Human tumors; Isolevuglandins; Lipid peroxidation