A5075037289- Carcinogens and Genotoxicity Assessment
- DNA Repair Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Pharmacogenetics and Drug Metabolism
- Mass Spectrometry Techniques and Applications
- DNA and Nucleic Acid Chemistry
- Drug Transport and Resistance Mechanisms
- Radioactive contamination and transfer
- Toxic Organic Pollutants Impact
- Glutathione Transferases and Polymorphisms
- Bladder and Urothelial Cancer Treatments
- Polyamine Metabolism and Applications
- Cancer therapeutics and mechanisms
- Hops Chemistry and Applications
- Radiation Effects and Dosimetry
- Effects and risks of endocrine disrupting chemicals
- Cystic Fibrosis Research Advances
- Metabolism and Genetic Disorders
- Neonatal Health and Biochemistry
- Estrogen and related hormone effects
- Isotope Analysis in Ecology
- Water Treatment and Disinfection
- Research Data Management Practices
- RNA modifications and cancer
- Inhalation and Respiratory Drug Delivery
Lawrence Livermore National Laboratory
2004-2025
Central Arkansas Veterans Healthcare System
2007
University of Arkansas for Medical Sciences
2007
University of California, Davis
2004
Abstract We conducted a study to evaluate dietary chemopreventive strategies reduce genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP IQ are heterocyclic amines (HCAs) that found in cooked meat may be risk factors for cancer. Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered low dose [14C] PhIPand [3H]...
Naphthalene is a ubiquitous combustion product and environmental contaminant with known human exposure. Chronic exposure to naphthalene vapor leads respiratory tumor formation in rodents. forms DNA adducts (precursors genotoxicity) tissue explants but it unclear if this occurs vivo. Wild-type C57BL/6 mice were orally exposed 50 mg/kg 14C-naphthalene. Naphthalene-DNA detected by accelerator mass spectrometry at 2-72 hours post-exposure both lung liver, decreasing abundance over time. Adducts...
Abstract Epidemiologic evidence indicates that exposure to heterocyclic amines in the diet is an important risk factor for development of colon cancer. Well-done cooked meats contain significant levels amines, which have been shown cause cancer laboratory animals. To better understand mechanisms amine bioactivation humans, most mass abundant amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used assess relationship between PhIP metabolism and DNA adduct formation. Ten human...
2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclicamine in the human diet and is carcinogenic rat prostate. To validate PhIP-induced prostatic neoplasia model of prostate cancer progression, we sought to study earliest histologic morphologic changes follow progressive over time. We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm) or control diets for 20 weeks, then sacrificed animals histomorphologic examination...
The technique of accelerator mass spectrometry (AMS) was validated successfully and used to study the pharmacokinetics disposition in dogs a preclinical drug candidate (7-deaza-29-<i>C</i>-methyl-adenosine; Compound A), after oral intravenous administration. primary objective this examine whether A displayed linear kinetics across subpharmacological (microdose) pharmacological dose ranges an animal model, before initiation human microdose study. AMS-derived properties were comparable data...
Abstract Ethylene oxide (EO) is widely used in the chemical industry and also formed humans through metabolic oxidation of ethylene, generated during physiologic processes. EO classified as a human carcinogen direct acting alkylating agent, primarily forming N7-(2-hydroxyethyl)guanine (N7-HEG). To conduct accurate risk assessments, it vital to ascertain relative contribution endogenously versus exogenously derived DNA damage identify sources background lesions. We have therefore defined vivo...
Abstract Tamoxifen is widely prescribed for the treatment of breast cancer and also licensed in United States prevention this disease. However, tamoxifen therapy associated with an increased occurrence endometrial women, there evidence that it may elevate risk colorectal cancer. The underlying mechanisms responsible tamoxifen-induced carcinogenesis women have not yet been elucidated, but much interest has focused on role DNA adduct formation. We investigated propensity to bind irreversibly...
UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of many different chemicals. Glucuronidation is especially important for detoxifying reactive intermediates from metabolic reactions, which otherwise can be biotransformed into highly cytotoxic or carcinogenic species. Detoxification certain food-borne-carcinogenic heterocyclic amines (HAs) dependent on UGT1A-mediated glucuronidation. 2-Amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP), most mass abundant HA found in...
Subetadex-α-methyl (SBX-Me), a modified, polyanionic cyclodextrin scaffold, has been evaluated for its utilization as medical countermeasure (MCM) to neutralize the effects of fentanyl and related opioids. Initial in vitro toxicity assays demonstrate that SBX-Me nontoxic profile, comparable FDA-approved cyclodextrin-based drug Sugammadex. Pharmacokinetic analysis showed rapid clearance with an elimination half-life ∼7.4 h little accumulation major organs. was also ability counteract...
Abstract Accelerator mass spectrometry (AMS) is currently one of the most sensitive methods available for trace detection DNA adducts and particularly valuable measuring in humans or animal models. However, standard approach requires administration a radiolabeled compound. As an alternative, we have developed preliminary 14 C‐postlabeling assay highly mutagenic O 6 ‐methyldeoxyguanosine (O ‐MedG), by AMS. Procedures were derivatising ‐MedG using unlabeled acetic anhydride. Using conventional...
<b>Abstract ID 93053</b> <b>Poster Board 412</b> Naphthalene is a ubiquitous environmental contaminant to which humans are exposed through variety of combustion events including smoking tobacco products, burning fossil fuels, and wildfires. Chronic exposure naphthalene vapor increases tumor formation in respiratory epithelium the mouse lung rat nose. Initial cytochrome P450-mediated bioactivation crucial precursor for toxic metabolites involved naphthalene's carcinogenic action. Our...