The importance of analyzing structure-activity relationships in mutagenicity studies

Shahin, Majdi M.

doi:10.1016/0165-1110(89)90034-1

Cited by 41 publications

(7 citation statements)

References 70 publications

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“…Lin and Solodar (127) also reported that p-phenylenediamine became mutagenic after it was oxidized. This finding suggests that p-phenylenediamine may not be mutagenic but became mutagenic after oxidation (130). Watanabe et al (133) discovered that p-phenylenediamine became strongly mutagenic in Salmonella typhimurium tester strain TA1538 in the presence of microsomal fraction following oxidation by H 2 O 2 .…”

Section: -Aminobiphenylmentioning

confidence: 99%

“…IACR classified benzidine and dyes metabolized to benzidine as category 1carcinogens (114). p-Phenylenediamine was reported to be non-mutagenic (126,127); but Shahin et al (128)(129)(130) reported it to be a weak mutagen. Chung et al (131) studied the mutagenicity of p-phenylenediamine and found it to be weakly mutagenic to Salmonella tester strain TA98 with metabolic activation.…”

Section: -Aminobiphenylmentioning

confidence: 99%

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Occurrence uses and carcinogenicity of arylamines

Chung¹

2015

Front Biosci

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Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

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Section: -Aminobiphenylmentioning

confidence: 99%

Section: -Aminobiphenylmentioning

confidence: 99%

Occurrence uses and carcinogenicity of arylamines

Chung¹

2015

Front Biosci

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“…Aromatic diamino compounds, e.g., 4,4′-methylenebis-(2-chloroaniline) (MOCA) 1 and 4,4′-methylenedianiline (MDA) (Chart 1), are used as curing agents in the production of polyurethane elastomers. Most compounds with the MDA structure are mutagenic and carcinogenic (1)(2)(3). MDA (4), 4,4′-methylenebis(2-methylaniline), 4,4′methylenebis(2-ethylaniline), 4,4′-methylenebis(2-fluoroaniline), MOCA (5), 4,4′-ethylenedianiline (EDA) (6), 4,4′-oxydianiline (ODA), and 4,4′-thiodianiline (TDA) (4) are mutagenic in Salmonella typhimurium TA98 (7).…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin Binding of Bicyclic Aromatic Amines

Sabbioni

Schutze

1998

Chem. Res. Toxicol.

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Aromatic diamino compounds, e.g., 4,4'-methylenebis(2-chloroaniline) (MOCA) and 4,4'-methylenedianiline (MDA), are used as curing agents in the production of elastomers. Since MOCA and MDA are mutagenic and carcinogenic, substitutes are of great commercial interest. For benzidine it has been shown that ortho substitution with methyl groups yields the nonmutagenic 3,3',5,5'-tetramethylbenzidine. Therefore, MDA analogues with large substituents in the ortho position have been synthesized. The substituents are supposed to inhibit the formation of the N-hydroxyarylamines which are the putative genotoxic intermediates. We investigated the biological availability of the N-hydroxylamines of ortho-substituted diamines and of known carcinogenic diamines in female Wistar rats, by determining hemoglobin (Hb) adducts. Hb from rats dosed with 0.5 mmol/kg diamine and from controls was isolated and hydrolyzed in base. The released diamine and monoacetyldiamine were quantified by HPLC with electrochemical detection and/or GC/MS. MDA, 4,4'-oxydianiline (ODA), 4,4'-ethylenedianiline, and 4,4'-thiodianiline (TDA) bound to hemoglobin as diamine and as monoacetyl-diamine. 4,4'-Methylenebis(2,6-dimethylaniline), 4,4'-methylenebis(2,6-diethylaniline), MOCA, and 4,4'-sulfonyldianiline (dapsone) bound only as diamine to Hb. 4,4'-Methylenebis(2,6-dichloroaniline) did not bind to Hb. Thus, the presence of two substituents in the ortho position and the presence of electron-withdrawing groups in the para position to the amino group drastically reduced the formation of Hb adducts. The amount of hemoglobin adducts was compared to their carcinogenic potency. The extent of hemoglobin binding of the bicyclic diamines (dapsone, 3,3'-dichlorobenzidine, MDA, MOCA, TDA, ODA, and benzidine) increases with their carcinogenic potency.

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“…The establishment of structure-activity relationships between aflatoxin-related molecules and the mutagenic and carcinogenic effects elicited by this class of compounds has been a subject of active research (Wong and Hsieh, 1976;Shahin, 1989). However, for molecules bearing the furobenzofuran moiety, all of these studies had so far to be restricted to the parent compounds since the corresponding epoxy derivatives, postulated as the ultimate species responsible for the mutagenicity exhibited by these mycotoxins, were still unknown.…”

Section: Introductionmentioning

confidence: 99%