Benzopyrene

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Benzopyrene
Benzopyrene
Chemical name Benzo[a]pyrene
Chemical formula C20H12
Molecular mass 252.31 g/mol
CAS number [50-32-8] [1]
Density 1.24 g/cm3
Melting point 179 °C
Boiling point 495 °C
SMILES c1\cc2\cc/cc3ccc4cc5ccccc5c1c4c23
Disclaimer and references

Benzo[a]pyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon that is mutagenic and highly carcinogenic. It is a crystalline yellow solid. Benzo[a]pyrene is a product of incomplete combustion at temperatures between 300 and 600°C. Is found in coal tar, in automobile exhaust fumes (especially from diesel engines), tobacco smoke, and in charbroiled food. Recent studies have revealed that levels of benzo[a]pyrene in burnt toast are significantly higher than once thought, although it is unproven whether burnt toast is itself carcinogenic.

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[edit] Consequences of Benzo[a]pyrene

A huge number of studies over the previous three decades have documented links between benzo[a]pyrene and cancers. It has been more difficult to link cancers to specific benzo[a]pyrene sources, especially in humans. Researchers at Kansas State University recently discovered a link between vitamin A and emphysema in smokers. Benzo[a]pyrene was found to be the link to the deficiency, since it induces vitamin A deficiency in rats.

On October 18, 1996, a study was published that provided the first true molecular evidence conclusively linking components in tobacco smoking to lung cancer. A chemical found in tobacco smoking, benzo[a]pyrene, was shown to cause genetic damage in lung cells that is identical to the damage observed in the DNA of most malignant lung tumours.

A 2001 National Cancer Institute study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue, particularly steaks, chicken with skin, and hamburgers. Japanese scientists showed that cooked beef contains mutagens, chemicals that are capable of altering the chemical structure of DNA.

[edit] Interaction with DNA

Chemical structure of the carcinogen benzopyrene diol epoxide
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Chemical structure of the carcinogen benzopyrene diol epoxide

Benzo[a]pyrene diol epoxide ((+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) is the carcinogenic product of three enzymatic reactions. Benzo[a]pyrene is first activated by cytochrome P4501A1 to form (+)-benzo[a]pyrene 7,8-oxide among other products. Next, (+)-benzo[a]pyrene 7,8-oxide is metabolized by epoxide hydrolase to yield (-)-benzo[a]pyrene-7,8,dihydrodiol. (-)-benzo[a]pyrene-7,8,dihydrodiol forms the ultimate carcinogen after reacting with cytochrome P4501A1 to yield benzopyrene diol epoxide ((+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The two carbons of the epoxide are electrophilic, due to an unequal sharing of electrons with the oxygen. As a result, this molecule intercalates in DNA, covalently bonding to the nucleophilic guanine nucleobases at the N2 position. A recent X-ray crystallography study shows this distorts the DNA. This can disrupt the normal process of copying DNA, and may lead to cancer. This mechanism of action is similar to that of aflatoxin which binds to the N7 position of guanine.

Benzo[a]pyrene induces high concentrations of cytochrome P4501A1 (CYP1A1) by binding to the AhR (arylhydrocarbon receptor) in the cytosol. Upon binding the transformed receptor translocates to the nucleus where it dimerises with ARNT (arylhydrocarbon receptor nuclear traslocator) and then binds xenobiotic response elements (XREs) in DNA located upstream of certain genes. This process increases transcription of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production. This process is similar to induction of CYP1A1 by certain polychlorinated biphenyls and dioxins.

Recently, Benzo[a]pyrene has been found to activate a transposon, LINE1, in humans (see reference).

[edit] References

Vilius Stribinskis and Kenneth S. Ramos (2006). Activation of Human Long Interspersed Nuclear Element 1 Retrotransposition by Benzo(a)pyrene, an Ubiquitous Environmental Carcinogen. Cancer Res 2006; 66: (5).

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