Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes.

doi:10.1093/JNCI/69.3.725

Paper

Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes.

Published Sep 1, 1982 · A. Wood, W. Levin, R. Chang

Journal of the National Cancer Institute

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17

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0

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Abstract

As an approach for elucidation of structure activity relationships that underlie the exceptionally large difference in carcinogenic activity between benz[a]anthracene and 7,12-dimethylbenz[a]anthracene (7,12-DMBA), 11 methyl- and/or fluorine-substituted benz[a]anthracenes were evaluated for tumor-initiating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly applications of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate for 16-26 weeks. 7,12-DMBA was almost two orders of magnitude more active as a tumor-initiator than 7- and 12-methylbenz[a]anthracene. Methyl substitution at the 7- and 7,12-positions of benz[a]anthracene was significantly more effective in the enhancement of tumorigenic activity than fluorine substitution at these positions. Although 7-fluorobenz[a]anthracene, 12-fluorobenz[a]anthracene, and 7,12-difluorobenz[a]anthracene had only 0.15, 0.26, and less than 0.005 times the tumor-initiating activity of their respective methyl-substituted derivatives, they were severalfold more active than benz[a]anthracene. 7-Fluorobenz[a]anthracene was slightly less active than 12-fluorobenz[a]anthracene, whereas 7-methylbenz[a]anthracene was about twofold more than 12-methylbenz[a]anthracene. For 7,12-di-substituted benz[a]anthracenes, 7-methyl-12-fluorobenz[a]anthracene was more than twice as tumorigenic as 7-fluoro-12-methylbenz[a]anthracene, but each was individually more active than 7-methylbenz[a]anthracene and 12-methylbenz[a]anthracene, respectively. Both fluorinated compounds were much less active than 7,12-DMBA. Substitution of fluorine or methyl at the 5-position of 7-methylbenz[a]anthracene and substitution of fluorine at the 5-position of 12-methylbenz[a]anthracene dramatically reduced their tumorigenic activity.

Non-RCT

Animal Study

Study Snapshot

7,12-DMBA is two orders of magnitude more active as a tumor-initiator than 7- and 12-methylbenz[a]anthracene, with methyl substitution at 7- and 7,12-positions being more effective than fluorine substitution.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes.

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References

Citations

The Structural Basis for the Production of Cancer and Detoxification by Oxidized Metabolites of Mesoanthracenic Methylated and Non-Methylated Polynuclear Hydrocarbons: a Paradigm Shift

The structural basis for carcinogenesis by polynuclear aromatic hydrocarbons is a methyl group at the most reactive center, followed by hydroxylation and conjugation, with blocking methylation preventing cancer production.

Phototoxicity and Environmental Transformation of Polycyclic Aromatic Hydrocarbons (PAHs)—Light-Induced Reactive Oxygen Species, Lipid Peroxidation, and DNA Damage

Photoreaction of environmental PAHs can cause lipid peroxidation and DNA damage, potentially promoting human skin damage and ageing.

Quantum chemical studies on ultimate carcinogenic metabolites from polycyclic aromatic hydrocarbons.

Recent quantum chemical studies on ultimate carcinogenic metabolites from polycyclic aromatic hydrocarbons reveal structure-activity relationships and correlations between experimental mutagenic potencies and calculated properties.

BIOALKYLATION OF BENZ(A)ANTHRACENE: IMPLICATIONS FOR CARCINOGENESIS

Metabolic activation of benz(a)anthracene in rat liver cytosol leads to the formation of methylated derivatives, which may have implications for carcinogenesis.

Carbocations from oxidized metabolites of benzo[a]anthracene: a computational study of their methylated and fluorinated derivatives and guanine adducts.

Bay-region carbocations in benzo[a]anthracene derivatives are more stable and bioactive than those formed via zwitterion formation, single electron oxidation, or benzylic hydroxylation.