Lack of mutagenicity to S. typhimurium of neopentyl bromide and pentaerythrityl tetrachloride: relation to chemical structure

Ashby, John; Callander, R.D.; Gilman, David J.

doi:10.1016/0165-7992(84)90045-9

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…Many mutagenic agents afford positive results in the NBP assay (epoxides, lactones, N-nitroso compounds, ethyleneimines, halogenated compounds, alkyl sulfonic esters...), whereas many nonmutagens or noncarcinogens show no response. 55 Thus, NBP was proposed as a reagent for the search for quantitative, semiquantitative, or simply qualitative correlations between alkylating activity and biological effects (carcinogenicity, mutagenicity, toxicity...). Kim and Thomas have suggested that "... the test may prove to be a simple, non-biological indicator of carcinogenic risks", 4 and as such, the NBP assay has been applied as an alert system to assay new compounds whose in vivo effects are unknown.…”

Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

“…It should be noted that this conclusion only applies to the tested compound itself; if the effective alkylating agent is formed during the metabolism of the compound studied, the NBP assay is useless unless it is carried out in simulated metabolic conditions. This absence of reactivity with NBP has been correlated with the lack of mutagenicity (e.g., neopentyl bromide and pentaerythrityl tetrachloride 55 or DDNU-oxide, a presumed metabolite of DDT). 42 It has also helped to understand the low alkylating potential attributed to weak electrophiles such as sorbic acid 9 and sorbates, 8 and acrylamide 12 and other α−β unsaturated carbonyls.…”

Section: Scheme 3 Generic Alkylation Mechanismmentioning

confidence: 99%

“…Higher temperatures are used to dissolve the reagents in less volatile solvents such as acetophenone and ethylene glycol . Ethylene glycol has the additional advantage of preventing the formation of separate organic and aqueous phases, as often occurs. ,− The method introduced by Preussman uses glycol monomethyl ether as solvent, and piperidine has been used extensively as a base. − …”

Section: Development Of the Nbp Assaymentioning

confidence: 99%

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Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Gómez‐Bombarelli

González‐Pérez

Calle

et al. 2012

Chem. Res. Toxicol.

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Alkylating agents are considered to be archetypal carcinogens. One suitable technique to evaluate the activity of alkylating compounds is the NBP assay. This method is based on the formation of a chromophore in the reaction between the alkylating agent and the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases. NBP is known to react with strong and weak alkylating agents, and much insight into such alkylation mechanisms in vivo can be gained from kinetic study of some alkylation reactions in vitro. Since 1925, the NBP assay has evolved from being a qualitative, analytical tool to becoming a useful physicochemical method that not only allows the rules of chemical reactivity that govern electrophilicity and nucleophilicity to be applied to the reaction of DNA with alkylating agents but also helps to understand some significant relationships between the structure of many alkylation substrates (including DNA) and their chemical and biological responses. Given that advances in this area have the potential to yield both fundamental and practical advances in chemistry, biology, predictive toxicology, and anticancer drug development, this review is designed to provide an overview of the evolution of the NBP method from its early inception until its recent kinetic–mechanistic approach, which allows the pros and cons of NBP as a DNA-model to be analyzed. The validity of NBP as a nucleophilicity model for DNA in general and the position of guanosine at N7 in particular are discussed.

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Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

Section: Scheme 3 Generic Alkylation Mechanismmentioning

confidence: 99%

Section: Development Of the Nbp Assaymentioning

confidence: 99%

See 2 more Smart Citations

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Gómez‐Bombarelli

González‐Pérez

Calle

et al. 2012

Chem. Res. Toxicol.

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“…The high degree of substitution at C2 in TBNPA confers resistance to biodegradation (10). Together with its high solubility in water (2 g/L at 25 °C) (11), TBNPA is considered among the most rapidly transported and minimally retarded contaminants.…”

Section: Introductionmentioning

confidence: 99%

Chemical Transformation of 3-Bromo-2,2-bis(bromomethyl)propanol under Basic Conditions

Ezra

Feinstein

Bilkis

et al. 2004

Environ. Sci. Technol.

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The mechanism of the spontaneous decomposition of 3-bromo-2,2-bis(bromomethyl)propanol (TBNPA) and the kinetics of the reaction of the parent compound and two subsequent products were determined in aqueous solution at temperatures from 30 to 70 degrees C and pH from 7.0 to 9.5. TBNPA is decomposed by a sequence of reactions that form 3,3-bis(bromomethyl)oxetane (BBMO), 3-bromomethyl-3-hydroxymethyloxetane (BMHMO), and 2,6-dioxaspiro[3.3]-heptane (DOH), releasing one bromide ion at each stage. The pseudo-first-order rate constant of the decomposition of TBNPA increases linearlywith the pH. The apparent activation energy of this transformation (98+/-2 KJ/mol) was calculated from the change of the effective second-order rate constant with temperature. The pseudoactivation energies of BBMO and BMHMO were estimated to be 109 and 151 KJ/mol, respectively. Good agreement was found between the rate coefficients derived from changes in the organic molecules concentrations and those determined from the changes in the Br- concentrations. TBNPA is the most abundant semivolatile organic pollutant in the aquitard studied, and together with its byproducts they posess an environmental hazard. TBNPA half-life is estimated to be about 100 years. This implies that high concentrations of TBNPA will persist in the aquifer long after the elimination of all its sources.

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The Weak Mutagenicity of CDA to Strain TA98 of Salmonella typhimurium

Ashby¹,

Callander²,

Paton³

1985

Comparative Genetic Toxicology

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Lack of mutagenicity to S. typhimurium of neopentyl bromide and pentaerythrityl tetrachloride: relation to chemical structure

Cited by 7 publications

References 9 publications

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Chemical Transformation of 3-Bromo-2,2-bis(bromomethyl)propanol under Basic Conditions

The Weak Mutagenicity of CDA to Strain TA98 of Salmonella typhimurium

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