Tumor-initiating ability of the twelve monomethylbenz[a]-anthracenes

Wislocki, Peter G.; Fiorentini, Karen M.; Fu, Peter P.; Yang, Shen K.; Lu, Anthony Y. H.

doi:10.1093/carcin/3.2.215

Cited by 49 publications

(41 citation statements)

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“…The authors point out that in the previous study of Wislocki et al (1982), in which 9,10-diMA was not carcinogenic, mice received only a single, lower dose of 9,10-diMA than in the present study.…”

Section: Alkylated Aromatic Hydrocarbonscontrasting

confidence: 53%

“…1-, 2-, 3-, 4-or 9-methylphenanthrene. Groups of 7-week old female CD-1 mice, 30 per group, were treated topically with various doses of a range of monomethylated derivatives of anthracene in acetone, followed by promotion with TPA. Mice received a single dose of the hydrocarbons followed, 1 week later, by twice weekly doses of TPA for 21 weeks (Wislocki et al, 1982).…”

Section: Alkylated Aromatic Hydrocarbonsmentioning

confidence: 99%

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Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

107

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Consumers are exposed to a range of mineral oil hydrocarbons (MOH) via food. Mineral oil saturated hydrocarbons (MOSH) consist of linear and branched alkanes, and alkyl-substituted cyclo-alkanes, whilst mineral oil aromatic hydrocarbons (MOAH) include mainly alkyl-substituted polyaromatic hydrocarbons. Products, commonly specified according to their physico-chemical properties, may differ in chemical composition depending on the oil source. Technical grade MOH contain 15 -35 % MOAH, which is minimised in food grade MOSH (white oils). Major sources of MOH in food are food packaging and additives, processing aids, and lubricants. Estimated MOSH exposure ranged from 0.03 to 0.3 mg/kg b.w. per day, with higher exposure in children. Specific production practices of bread and grains may provide additional MOSH exposure. Except for white oils, exposure to MOAH is about 20 % of that of MOSH. Absorption of alkanes with carbon number above C 35 is negligible. Branched and cyclic alkanes are less efficiently oxidised than n-alkanes. MOSH from C 16 to C 35 may accumulate and cause microgranulomas in several tissues including lymph nodes, spleen and liver. Hepatic microgranulomas associated with inflammation in Fischer 344 rats were considered the critical effect. The no-observed-adverse-effect level for induction of liver microgranulomas by the most potent MOSH, 19 mg/kg b.w. per day, was used as a Reference Point for calculating margins of exposure (MOEs) for background MOSH exposure. MOEs ranged from 59 to 680. Hence, background exposure to MOSH via food in 1 On request from the European Commission, Question No EFSA-Q-2010-00170, adopted on 3 May 2012. 2 SUMMARYFollowing a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on mineral oil hydrocarbons (MOH) in Food. Mineral oil hydrocarbons occur in food both as a result of contamination and from various intentional uses in food production. In order to assess the need for possible regulatory measures as regards MOH in food, EFSA was requested to assess the risks related to their occurrence in food. More specifically, the opinion should evaluate whether new toxicity data are available and whether the current acceptable daily intakes (ADIs) are still applicable, explore whether certain classes (or subclasses) of MOH are more relevant due to their toxicity or to differences in the way they are metabolised by the human body, and identify the different background sources, other than from adulteration or misuse, of MOH occurrence in food. In addition a dietary exposure assessment was requested for the general population and for specific subgroups of the population (e.g. infants, children and people following specific diets), by taking into account the background occurrence of MOH in food. Included in the request was also to advise on MOH and food classes to be included if monitoring were to be set up for their presence in food.The scientific literature and other sources were s...

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Section: Alkylated Aromatic Hydrocarbonscontrasting

confidence: 53%

Section: Alkylated Aromatic Hydrocarbonsmentioning

confidence: 99%

Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

107

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“…Among benzo [a]anthracenes (BAs), the unsubstituted parent compound presents borderline activity (5), but 7-methylbenzo[a] anthracene (7-MBA) is considerably more active (it is the strongest tumor initiator among the twelve possible monomethylated BAs, followed by the 6-CH 3 , 8-CH 3 , and 12-CH 3 derivatives) (6)(7)(8)(9), while 7,12-dimethylbenzo[a]anthracene (7, is one of the most potent carcinogens known (10). On the other hand, low tumorigenicity has been observed for 1-, 2-, 3-and 4-MBA (6). Among other dimethyl-BA compounds, the 6,8-dimethyl-and 8,9-dimethyl-BA have also been reported to have relatively high activity (4).…”

Section: Introductionmentioning

confidence: 99%

Carbocations from Oxidized Metabolites of Benzo[a]anthracene: A Computational Study of Their Methylated and Fluorinated Derivatives and Guanine Adducts

Borosky

Laali

2006

Chem. Res. Toxicol.

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Structure-reactivity relationships and substituent effects on carbocation stability in benzo [a] anthracene (BA) derivatives have been studied computationally at the B3LYP/6-31G* and MP2/6-31G** levels. Bay-region carbocations are formed by O-protonation of the 1,2-epoxides in barrierless processes. This process is energetically more favored as compared to carbocation generation via zwitterion formation/O-protonation, via single electron oxidation to generate a radical cation, or via benzylic hydroxylation. Relative carbocation stabilities were determined in the gas phase and in water as solvent (PCM method). Charge delocalization mode in the BA carbocation framework was deduced from NPA-derived changes in charges, and substitution by methyl or fluorine was studied at different positions selected on basis of the carbocation charge density. A bayregion methyl group produces structural distortion with consequent deviation from planarity of the aromatic system, which destabilizes the epoxide, favoring ring opening. Whereas fluorine substitution at sites bearing significant positive charge leads to carbocation stabilization by fluorine p-π back-bonding, a fluorine atom at a ring position which presented negative charge density leads to inductive destabilization. Methylated derivatives are less sensitive to substituent effects as compared to the fluorinated analogues. Although the solvent decreases the exothermicity of the epoxide ring opening reactions due to greater stabilization of the reactants, it provokes no changes in relative reactivities. Relative energies in the resulting bay-region carbocations are examined taking into account the available biological activity data on these compounds. In selected cases, quenching of bay-region carbocations was investigated by analyzing relative energies (in the gas phase and in water) and geometries of their guanine adducts formed via covalent bond formation with the exocyclic amino group and with the N-7.

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“…1-Hydroxybenzo[a]pyrene (1-HOBaP) was purchased from NCI Chemical Carcinogen Reference Standard Repositories (Kansas City, USA). 5-, 6-, 7-Methylbenz[a]anthrancenes (MBA) were synthesized as described before (21,22). All stock solutions (1 mM) were prepared in N,N-dimethylformamide (DMF) or methanol and stored in the refrigerator with the exclusion of light.…”

Section: Reagents Chemicals and Instrumentationmentioning

confidence: 99%

Effects of Histidine on Light-Induced DNA Single-Strand Cleavage by Selected Polycyclic Aromatic Hydrocarbons

Dong

Hwang

et al. 2002

Polycyclic Aromatic Compounds

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have been shown to cause DNA cleavage, at least partially, by generating singlet oxygen. Therefore, the presence of histidine, a singlet oxygen quencher, should inhibit the DNA photocleavage. However, the presence of 50 mM histidine greatly enhances the DNA photocleavage caused by these compounds. This effect is due to the inhibition of the photodegradation of the PAH compounds. Therefore, care must be taken when interpreting the singlet oxygen quenching data by histidine. Histidine may coexist with PAHs that have entered the body. The presence of histidine can alter the photochemical reaction and, possibly, the phototoxicity mechanism of the PAHs.

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Tumor-initiating ability of the twelve monomethylbenz[a]-anthracenes

Cited by 49 publications

References 0 publications

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Carbocations from Oxidized Metabolites of Benzo[a]anthracene: A Computational Study of Their Methylated and Fluorinated Derivatives and Guanine Adducts

Effects of Histidine on Light-Induced DNA Single-Strand Cleavage by Selected Polycyclic Aromatic Hydrocarbons

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