In vitro evaluation of some derivatives of the carcinogen butter yellow: implications for environmental screening

Ashby, John; Styles, J.A.; Paton, David M.

doi:10.1038/bjc.1978.161

Cited by 45 publications

(6 citation statements)

References 23 publications

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“…Replacement of the dimethylamino group of 4-dimethylaminoazobenzene by a diethylamino or a higher dialkylamino group has been shown to lead to a marked attenuation of its carcinogenicity 28 and mutagenicity. 29 Ring substituents other than amino or aminogenerating groups have been reported to modulate aromatic amines carcinogenicity mainly by steric effects: the larger the substituents (especially in the ortho position), the less potent the chemical. 5 On the contrary, the substitution of a chloro group or a methyl/methoxy group ortho to the amino group often enhances activity.…”

Section: Qualitative Notions On the Structure−activity Relationships ...mentioning

confidence: 99%

“…Even the nature and position of the amine or of the amine-generating group influences the carcinogenic potential at the level of bioactivation step: for example, for dialkylamino groups with bulky or long alkyl substitution, N -dealkylation does not readily occur to allow further bioactivation. Replacement of the dimethylamino group of 4-dimethylaminoazobenzene by a diethylamino or a higher dialkylamino group has been shown to lead to a marked attenuation of its carcinogenicity and mutagenicity …”

Section: Qualitative Notions On the Structure−activity Relationships ...mentioning

confidence: 99%

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Quantitative Structure−Activity Relationships of Mutagenic and Carcinogenic Aromatic Amines

et al. 2000

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Section: Qualitative Notions On the Structure−activity Relationships ...mentioning

confidence: 99%

Section: Qualitative Notions On the Structure−activity Relationships ...mentioning

confidence: 99%

Quantitative Structure−Activity Relationships of Mutagenic and Carcinogenic Aromatic Amines

et al. 2000

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“…The nature of the amine-generating groups is important, since for dialky amino groups with bulky or long alkyl substitution N-dealkylation does not readily occur to allow further bioactivation. Replacement of the dimethylamino (-NMe^ group of 4-dimethylaminoazobenzene by a diethylarnino (-NEt^ or a higher dialkylamino group has been shown to lead to marked attenuation of its carcinogenicity (11) and mutagenicity (22).…”

Section: Nature Of Amine/amine-generating Group(s)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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“…Moreover, the results indicate the difficulty in estimating the actual mutagenic capacity of a compound in a simple system and in donating a value to this mutagenic activity. The implication of these results for the relevance of microbial test systems has already been raised (Ashby and Styles, 1978).…”

Section: New Prioritiesmentioning

confidence: 95%

Invitation Paper: Can Mutation Theories of Carcinogenesis Set Priorities for Carcinogen Testing Programs?

Stich¹,

Acton²

1979

Can. J. Genet. Cytol.

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The recent activity in designing, validating and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation between the carcinogenicity and mutagenicity of chemicals and by the assumption that mutations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from man's environment, and would lead the public to avoid them. The actual response, however, is quite different. Government departments shy away from making any decisions on the basis of in vitro test systems, the public at large is becoming irritated by daily announcements that many of their cherished habits could adversely affect their health, and industries feel threatened and may reduce their search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to the uncertainty about the involvement of mutations in the formation of benign and malignant tumors. Following the initial rapid advances in the detection of environmental chemicals with carcinogenic and mutagenic properties, we seem to have arrived at the cross roads: we must now set new priorities for future research, and must make an unbiased assessment of the actual hazard of a compound to man and the human population.

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In vitro evaluation of some derivatives of the carcinogen butter yellow: implications for environmental screening

Cited by 45 publications

References 23 publications

Quantitative Structure−Activity Relationships of Mutagenic and Carcinogenic Aromatic Amines

Quantitative Structure−Activity Relationships of Mutagenic and Carcinogenic Aromatic Amines

Cancer Risk Reduction Through Mechanism-Based Molecular Design of Chemicals

Invitation Paper: Can Mutation Theories of Carcinogenesis Set Priorities for Carcinogen Testing Programs?

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