Metabolic activation routes of arylamines and their genotoxic effects.

Meerman, John H.N.; Poll, Monique L.M. van de

doi:10.1289/ehp.94102s6153

Cited by 14 publications

(2 citation statements)

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“…A large number of dietary pro-mutagens and pro-carcinogens are known to be bioactivated by SULTs, and the sulfation of those xenobiotics can result in the pathogenesis of gastrointestinal tumors. Examples of chemicals involved in sulfation for generation of DNA- and protein-adducting species include estragole, safrole, benzylic alcohols of polycyclic aromatic hydrocarbons, hydroxyarylamines and arylhydroxamic acids (Meerman & Van de Poll 1994; Miller 1994; Chou et al 1995; Wakazono et al 1998). All the investigated flavonoids in this study can act as inhibitors of SULTs present in human intestine.…”

Section: Discussionmentioning

confidence: 99%

Sulfation of dietary flavonoids by human sulfotransferases

et al. 2009

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Dietary flavonoids catechin, epicatechin, eriodictyol, and hesperetin were investigated as substrates and inhibitors of human sulfotransferases (hSULTs). Purified recombinant proteins and human intestine cytosol were used as enzyme sources. hSULT1A1 and hSULT1A3 as well as human intestine cytosol can catalyse the sulfation of the investigated flavonoids. Sulfation of catechin, epicatechin, eriodictyol, and hesperetin by recombinant hSULTs showed substrate inhibition at high flavonoid concentrations. Hesperetin and eriodictyol are potent inhibitors of purified hSULT1A1, hSULT1A3, hSULT1E1, and hSULT2A1. Catechin and epicatechin inhibited hSULT1A1 and hSULT1A3, but not hSULT1E1 and hSULT2A1. The sulfation efficacy and potency of inhibition is related to the C-ring structure of flavonoids. These results suggest that dietary flavonoids may regulate human SULT activity and, therefore, affect the regulation of hormones and neurotransmitters, detoxification of drugs, and the bioactivation of pro-carcinogens and pro-mutagens.

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Section: Discussionmentioning

confidence: 99%

Sulfation of dietary flavonoids by human sulfotransferases

et al. 2009

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“…The acyloxyamines are highly reactive and, upon departure of the acyloxy anion, the arylamidonium/arylnitrenium ion formed may readily bind covalendy to cellular nucleophiles such as DNA to initiate carcinogenesis (13,17). The glucuronides, on the other hand, are essentially unreactive and represent stable excretion products from the liver (the site of their formation).…”

Section: Bioactivation Mechanisms In Relation To Structural Criteria mentioning

confidence: 99%

Cancer Risk Reduction Through Mechanism-Based Molecular Design of Chemicals

Lai¹,

Woo²,

Argus³

et al. 1996

ACS Symposium Series

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Increased understanding of the mechanistic basis of chemical carcinogenesis and the relationship between molecular structure and carcinogenic activity provides opportunities not only for identifying suspect carcinogens but also for designing chemicals with lower carcinogenic potential. One of the chemical classes in which the structural and molecular basis of carcinogenicity is the most clearly understood is the aromatic amines. This paper summarizes the bioactivation mechanisms and structural criteria for aromatic amine carcinogenesis; a strategic approach of risk reduction through mechanism-based molecular design of aromatic amine dyes with lower carcinogenic potential is discussed. With our increasing knowledge of the mechanisms and structure-activity relationships, it should be possible to develop safer products for other chemical classes using similar molecular design approaches. Mechanisms of Chemical Carcinogenesis and Structure-Activity RelationshipsConsiderable knowledge of the mechanisms of chemical carcinogenesis has accrued since the pioneer work by James A. and Elizabeth C. Miller at the University of Wisconsin beginning in the 1940's, particularly concepts on the metabolic activation of chemicals to reactive electrophilic intermediates that interact with cellular nucleophiles to initiate carcinogenesis (7,2). For many carcinogen classes, the molecular basis of carcinogenic activity is now known in considerable detail and the concept of electrophiles provides the most probable rationale for their carcinogenic action. Some of the electrophilic, reactive intermediates believed to be responsible for the carcinogenicity of genotoxic chemicals include: carbonium, aziridium, episulfonium, oxonium, nitrenium or arylamidonium ions, free radicals, epoxides, lactones, aldehydes, semiquinones/quinoneimines, and acylating moieties. The metabolic activation of various genotoxic chemicals to their ultimate carcinogenic metabolites has been reviewed (3).

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Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

Darby

2023

Patty's Toxicology

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The fundamental aromatic hydrocarbon benzene, when substituted by one or more functional groups of the amine, nitro, or halogen classes, alone or in various combinations, provides an enormous number of compounds of immense practical value, ubiquitous presence in the industrial world, and often heightened toxicity relative to benzene itself, a notorious cause of blood cancer. This chapter begins by providing a general overview of aromatic compounds possessing amino and/or nitro substituents, with or without halogen substituents. The production and uses, exposure and biomonitoring, toxicity, and toxic mechanism of action are introduced. The remainder of the chapter focuses on specific compounds in a roughly systematic order based upon chemical structure, expanding on the same subheadings as covered in the general overview. The nomenclature of these compounds can be very confusing since many have traditional names that sometimes markedly differ from their systematized formal names. In this chapter, the same traditional names are used as were used in the previous edition of this publication, but if there is ambiguity of nomenclature, the Chemical Abstracts Service (CAS) numbers provided herein correspond to unique structures, each of which may have several names depending upon the naming convention. In general, when an aromatic compound has an amino or a nitro substituent, it is referred to as an “aniline” or a “nitrobenzene,” respectively, based upon the names of the parent compounds, even though other substituents may be present. When amino and nitro groups are present on the same benzene ring, “aniline” takes precedence, and both “aniline” and “nitrobenzene” take precedence over halogens. There are many exceptions to these general rules, however.

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Metabolic activation routes of arylamines and their genotoxic effects.

Cited by 14 publications

References 40 publications

Sulfation of dietary flavonoids by human sulfotransferases

Sulfation of dietary flavonoids by human sulfotransferases

Cancer Risk Reduction Through Mechanism-Based Molecular Design of Chemicals

Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

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