Macromolecular adducts caused by environmental chemicals

Abstract

We describe three biomonitoring studies in which hemoglobin (Hb) adducts were used as biochemical markers to assess indirectly the target dose of genotoxic chemicals. We monitored the exposure to 1,3-butadiene in occupationally exposed workers and in two control groups by analyzing the adducts formed by the reaction of the first activation product, butadiene monoepoxide, with the terminal valine of Hb; we also measured hydrolyzable adducts formed by the reaction of metabolically formed nitroso derivatives with Hb from five selected nitropolycyclic aromatic hydrocarbons (1-nitropyrene; 2-nitrofluorene, 3-nitrofluoranthrene, 6-nitrochrysene, and 9-nitrophenanthrene) in coke oven workers of different job categories and control workers of the same geographical area. We detected hydrolyzable adducts from monocyclic nitroarenes in blood from individuals living in a contaminated area where explosives had been produced and from controls. The contaminants considered were 2,4,6-trinitrotoluene; 2,4- and 2,6-dinitrotoluene; and 1,3-dinitrobenzene. Differences between groups were significant, but interindividual variation was great and back-ground exposures must be considered.

Biomonitoring Human Albumin Adducts: The Past, the Present, and the Future

“…1 The catabolism of Alb takes place primarily in muscle, skin, and the liver, resulting in a serum half-life of approximately 19−25 days. 1 Alb (UniProtKB -P02768) comprises 62 Glu, 62 Ala, 61 Leu, 59 Lys, 41 Val, 36 Asp, 35 Cys, 31 Phe, 28 Thr, 24 Ser, 24 Arg, 24 Pro, 20 Gln, 18 Tyr, 17 Asn, 16 His, 12 Gly, 6 Met, 8 Ile, and a single Trp residue. 2 The acidic amino acid residues exceed the basic ones, resulting in a high net negative net charge at physiological pH (62 Glu + 36 Asp versus 59 Lys + 24 Arg) which facilitates the solubility of Alb.…”

“…The reactivity of Hb with aromatic amines and production of methemoglobin by genotoxic arylhydroxylamines has also been well studied and reviewed. , Pereira et al showed a linear relationship between Hb-adducts and DNA-adducts for 2-acetylaminofluorene in mice and rats . Hb adduct formation for many aromatic amines occurs as a sulfinamide linkage formed by reaction of the arylnitroso intermediates with the β-Cys chain of Hb. − These adducts undergo hydrolysis with base or acid in vitro, and the liberated amines can be assayed by GC methods . The determination of arylamine-Hb adducts is a well established biomonitoring method and performed in many laboratories worldwide. ,,, In 1961, the toxic mold Aspergillus flavus containing aflatoxin B 1 (AFB) was discovered to be responsible for the outbreak of deaths of turkeys consuming contaminated meal in Britain. , The structure of AFB was elucidated by George Büchi, and its metabolism and DNA-adduct and protein adduct formation were largely carried out at the Massachusetts Institute of Technology in Cambridge (MA, USA) by Gerald Wogan and his colleagues. ,, …”

Biomarkers: Coming of Age for Environmental Health and Risk Assessment

“…This methodology has since evolved into a widely-used and highly sensitive technique for quantitating N-terminal Hb adducts of a variety of xenobiotic metabolites in human blood ( − ). Hb adducts have been employed as internal exposure biomarkers for aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons (PAHs), and other compounds ( − ).…”

A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons

“…This Hb adduct is usually stable in vivo but can be readily hydrolyzed in vitro to give corresponding amino-PAH (23–25). The resulting amino arenes are extracted and quantified using a GC-MS method (12, 26). We modified the previously published GC-MS method into a more sensitive HPLC-MS-MS method.…”