Highly sensitive immunoassays have been used to quantitate aflatoxins (AF) and N-nitrosamines (NNO) in human body fluids and tissues, respectively. This approach was taken in order to quantitate environmental exposure to these agents at an individual level to facilitate the investigation of their role in the etiology of human cancer. In order to analyse AF in human urine, an immunopurification step has been developed by using AF-specific antibody bound to AH-Sepharose 4B gel in a small (4-ml gel volume) affinity column prior to enzyme-linked immunosorbent assay (ELISA). The ELISA can be used to quantitate aflatoxin B1 (AFB1) over the range 0.01 ng/ml to 10 ng/ml and the assay system has been validated by using human urine samples spiked with AFB1 over this concentration range. In addition, 29 urine samples from the Philippines have been analysed and found to contain a range of levels from zero to 4.25 ng/ml AFB1 equivalent with a mean of 0.875 ng/ml. This compared with a mean of 0.066 ng/ml AFB1 equivalent in samples from France. Radioimmunoassay of O6-methyldeoxyguanosine (O6-medG) has been performed on human oesophageal and cardiac stomach mucosal DNA from tissue samples obtained during surgery in Linxian County, People's Republic of China, an area of high risk for both oesophageal and stomach cancer. Using the methodology described and having 1 mg of hydrolyzed DNA allows the detection of approximately 25 fmol O6medG per mg DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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http://dx.doi.org/10.1002/jcb.240300206 | DOI Listing |
Chem Res Toxicol
February 2024
Drug Safety Research and Development, Global Portfolio and Regulatory Strategy, Pfizer Worldwide Research, Development, and Medical, Groton, Connecticut 06340, United States.
A thorough literature review was undertaken to understand how the pathways of -nitrosamine transformation relate to mutagenic potential and carcinogenic potency in rodents. Empirical and computational evidence indicates that a common radical intermediate is created by CYP-mediated hydrogen abstraction at the α-carbon; it is responsible for both activation, leading to the formation of DNA-reactive diazonium species, and deactivation by denitrosation. There are competing sites of CYP metabolism (e.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
June 2023
Xiphora Biopharma Consulting, 9 Richmond Apartments, Redland Court Road, Bristol, BS6 7BG, UK. Electronic address:
The TTC (Threshold of Toxicological Concern; set at 1.5 μg/day for pharmaceuticals) defines an acceptable patient intake for any unstudied chemical posing a negligible risk of carcinogenicity or other toxic effects. A group of high potency mutagenic carcinogens, defined solely by the presence of particular structural alerts, are referred to as the "cohort of concern" (CoC); aflatoxin-like-, N-nitroso-, and alkyl-azoxy compounds are considered to pose a significant carcinogenic risk at intakes below the TTC.
View Article and Find Full Text PDFRep Carcinog
December 2021
Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Background: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology Program (NTP) prepares for the U.S. Department of Health and Human Services Secretary.
View Article and Find Full Text PDFHepat Med
January 2021
Hematologist-Oncologist, Allegheny Health Network, Pittsburgh, PA 15212, USA.
Primary liver cancer has the sixth highest incidence and fourth highest cancer mortality worldwide. Hepatitis B is the leading cause of liver cancer, though its incidence is decreasing with vaccination. Alcohol is the leading cause of liver transplant, cirrhosis, and cancer in the developed world, and is projected to surpass hepatitis B as the leading hepatic cancer etiology worldwide.
View Article and Find Full Text PDFBr J Nutr
September 2008
Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy.
In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts.
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