Benzopyrene

Shopping on line can be easy, simple and save you lots of money. It can also take a lot of your time, frustrate you, and result in unwanted purchases. Now the same can be said for regular high street shopping, but with the vast opportunity presented by the Internet it will pay you to spend a few minutes reading this and understanding how to better optimize your Benzopyrene shopping experience:

1. Compare - without doubt the biggest advantage that the Benzopyrene offers shoppers today is the ability to compare thousands of Benzopyrene at a time. This is a great thing, but not necessarily all the time! Too much can be daunting at times so take advantage of the great comparison sites and where possible let them do the hard work for you.

2. Research - if it has been said it will be on the internet. Ignorance is no longer a justifiable reason for buying the wrong thing. Take the time to research in detail everything that you could possible want to know about

3. Testimonials - don't know anybody that has bought a Benzopyrene? Wrong! If the Benzopyrene is good the internet will let you know. Use the Internet as a friend and get testimonials before you buy.

4. Questions - Got a question about Benzopyrene then search the Forums, FAQ's, Blogs etc. Don't be afraid to ask .....

5. Reputation - Never heard of the company selling Benzopyrene? Don't worry, no reason why you should know every company in the world, but you know someone that does! Use the internet to find out what people are saying about Benzopyrene and build up a picture of their reputation for sales, returns, customer service, delivery etc.

6. Returns - still worried that even after all of the above your Benzopyrene wont be what you want? Check out the returns policy. There is so much competition now that someone, somewhere is bound to offer the terms that you are comfortable with.

7. Feedback - happy with your Benzopyrene then let people know, after all you are depending on others people input in your buying decision, so why not give a little back.

8. Security - check for the yellow padlock on the Benzopyrene site before you buy, and the s after http:/ /i.e. https:// = a secure site

9. Contact - got a question about Benzopyrene, or want to leave a comment then check out the sites contact page. Reputable companies have them and respond.

10. Payment - ready to pay for your Benzopyrene, then use your credit card or PayPal! Be aware of companies that don't accept them, there may be genuine reasons but given the huge amount of choice you have when buying online there is no reason at all not to buy via credit card or PayPal.

{{Chembox new| Name = Benzopyrene| ImageFile = Benzo-a-pyrene.svg| ImageSize = 180px| ImageName = Benzopyrene| IUPACName = Benzopyrene| Section1 = {{Chembox Identifiers| SMILES = c1\cc2\cc/cc3ccc4cc5ccccc5c1c4c23 --> | Section2 = {{Chembox Properties| Formula = C20H12| MolarMass = 252.31 g/mol| Density = 1.24 g/cm³| MeltingPt = 179 °C| BoilingPt = 495 °C --> -->

Benzopyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon that is mutagenic and highly carcinogenic. It is a crystalline yellow solid. Benzopyrene is a product of incomplete combustion at temperatures between 300 and 600 °Celsius. Benzopyrene was determined in 1933 to be the component of coal tar responsible for the first recognized occupation-associated cancers, the sooty warts (cancers of the scrotum) suffered by chimney sweeps in 18th century England. In the 19th century, high incidences of skin cancers were noted among fuel industry workers. By the early 20th century, malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar.

Sources of Benzopyrene Benzopyrene is found in coal tar, in automobile exhaust fumes (especially from diesel engines), tobacco smoke, wood smoke, and in charbroiled food. Recent studies have revealed that levels of benzopyrene in burnt toast are significantly higher than once thought, although it is unproven whether burnt toast is itself carcinogenic.

Toxicity of Benzopyrene A vast number of studies over the previous three decades have documented links between benzopyrene and cancers. It has been more difficult to link cancers to specific benzopyrene sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion). Researchers at Kansas State University recently discovered a link between vitamin A and emphysema in smokers. Benzopyrene was found to be the link to the deficiency, since it induces vitamin A deficiency in rats.

In 1996, a study was published that provided the clear molecular evidence conclusively linking components in tobacco smoke to lung cancer. Denissenko MF, Pao A, Tang M, Pfeifer GP. Preferential formation of benzopyrene adducts at lung cancer mutational hotspots in P53. Science. 1996 October 18;274(5286):430-2. Benzopyrene, found in tobacco smoke, was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA of most malignant lung tumours.

A 2001 National Cancer Institute study found levels of benzopyrene 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 . However, the foods themselves are not necessarily carcinogenic, even if they contain trace amounts of carcinogens, because the gastrointestinal tract protects itself against carcinomas by shedding its outer layer continuously. Furthermore, detoxification enzymes, such as cytochrome P450 have increased activities in the gut due to the normal requirement for protection from food-borne toxins. Thus in most cases small amounts of benzopyrene are metabolized by gut enzymes prior to being passed on to the blood. The lungs are not protected in either of these manners.

A recent study has found that cytochrome P450 (CYP1A1) and cytochrome P450 (CYP1B1) are both protective and, confusingly, necessary for benzopyrene toxicity. Experiments with strains of mice engineered to remove (gene knockout) CYP1A1and CYP1B1 reveal that CYP1A1 primarily acts to protect mammals from low doses of benzopyrene, and that removing this protection causes the biological accumulation of large concentrations of benzopyrene. Unless CYP1B1 is also knocked out, benzopyrene toxicity results from the bioactivation of benzopyrene to the ultimate toxic compound, benzopyrene-7,8-dihydrodiol-9,10-epoxide (see below).Data presented by Daniel W. Nebert in research seminars 2007

Interaction with DNA , in an adduct to DNA.Created from PDB 1JDGProperly speaking, benzopyrene is a procarcinogen, meaning that the mechanism of carcinogensis of benzopyrene depends on enzymatic metabolism of benzopyrene to the ultimate mutagen, benzopyrene diol epoxide, pictured at right. This molecule Intercalation (chemistry) in DNA, covalent bond bonding to the nucleophile guanine nucleobases at the N2 position. X-ray crystallography and nuclear magnetic resonance structure studies show that this binding distorts the DNA,Volk DE, Thiviyanathan V, Rice JS, Luxon BA, Shah JH, Yagi H, Sayer JM, Yeh HJ, Jerina DM, Gorenstein DG. Solution structure of a cis-opened (10R)-N6-deoxyadenosine adduct of(9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzopyrene in a DNA duplex. Biochemistry. 2003 February 18;42(6):1410-20. inducing mutations by perturbing the double-helical DNA structure. This disrupts the normal process of copying DNA and induces mutations, which explains the occurrence of cancer after exposure. This mechanism of action is similar to that of aflatoxin which binds to the N7 position of guanine.Eaton DL, Gallagher EP. Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994;34:135-72.

There are indications that specifically benzopyrene diol epoxide specifically targets the protective p53 gene.Pfeifer GP, Denissenko MF, Olivier M, Tretyakova N, Hecht SS, Hainaut P. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene. 2002 October 21;21(48):7435-51. This gene is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. By inducing G (guanine) to T (thymidine) transversions in transversion hotspots within p53, there is a probability that benzopyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer.

Benzopyrene diol epoxide is the carcinogenic product of three enzymatic reactions: (1) Benzopyrene is first oxidized by Cytochrome P450 oxidase1A1 to form a variety of products, including (+)-benzopyrene 7,8-oxide.Shou M, Gonzalez FJ, Gelboin HV. Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase.Biochemistry. 1996 December 10;35(49):15807-13 (2) This product is metabolized by epoxide hydrolase, opening up the epoxide ring to yield (-)-benzopyrene-7,8,dihydrodiol. (3)The ultimate carcinogen is formed after another reaction with Cytochrome P450 oxidase1A1 to yield the benzopyrene-7,8-dihydrodiol-9,10-epoxide. It is this diol epoxide that covalently binds to DNA.

Benzopyrene induces Cytochrome P450 oxidase1A1 (CYP1A1) by binding to the AHR (aryl hydrocarbon receptor) in the cytosol.Whitlock JP Jr. Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol. 1999;39:103-25. Upon binding the transformed receptor translocates to the nucleus where it dimerises with ARNT (aryl hydrocarbon receptor nuclear translocator) and then binds xenobiotic response elements (XREs) in DNA located upstream of certain genes. This process increases Transcription (genetics) of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production.Whitlock JP Jr. Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol. 1999;39:103-25. This process is similar to induction of CYP1A1 by certain polychlorinated biphenyls and dioxins.

Recently, Benzopyrene has been found to activate a transposon, LINE1, in humansVilius 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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