Benzopyrene
Encyclopedia
Benzo[a]pyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon
whose metabolites are mutagen
ic and highly carcinogen
ic. Benzo[a]pyrene is listed as a Group 1 carcinogen by the IARC
. It belongs to a class of polycyclic aromatic compounds known as benzopyrene
s, which consist of a benzene
ring fused to a pyrene
molecule. Benzo[a]pyrene is a product of incomplete combustion
at temperature
s between 300 and 600 °C (572 and 1,112 °F). Benzo[a]pyrene 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, the toxicity of benzo[a]pyrene was demonstrated when malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar
. When the body's metabolism attempts to remove Benzo[a]pyrene by converting into a water soluble compound for easier excretion. The resulting diol epoxide, however, reacts with and binds to DNA resulting in mutations which can lead to cancer.
, in automobile exhaust fumes
(especially from diesel engine
s), in all smoke resulting from the combustion of organic material (including cigarette 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. Cooked meat products, regular consumption of which has been epidemiologically associated with increased levels of colon cancer (although this in itself does not prove carcinogenicity), have been shown to contain up to 4 ng/g of benzo[a]pyrene, and up to 5.5 ng/g in fried chicken and 62.6 ng/g in overcooked charcoal barbecued beef.
recently discovered a link between vitamin A
deficiency and emphysema
in smokers. Benzo[a]pyrene was found to be behind the link, 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
. Benzo[a]pyrene, found in tobacco smoke (including cigarette 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 benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue
, particularly steak
s, chicken
with skin, and hamburger
s. Japan
ese 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 carcinoma
s by shedding its outer layer continuously. Furthermore, detoxification enzymes, such as cytochromes 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 benzo[a]pyrene 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 1A1 (CYP1A1
) and cytochrome P450 1B1 (CYP1B1
) are both protective and, confusingly, necessary for benzo[a]pyrene toxicity. Experiments with strains of mice engineered to remove (knockout
) CYP1A1
and CYP1B1
reveal that CYP1A1 primarily acts to protect mammals from low doses of benzo[a]pyrene, and that removing this protection causes the biological accumulation of large concentrations of benzo[a]pyrene. Unless CYP1B1
is also knocked out, benzo[a]pyrene toxicity results from the bioactivation of benzo[a]pyrene to the ultimate toxic compound, benzo[a]pyrene -7,8-dihydrodiol-9,10-epoxide (see below).
Properly speaking, benzo[a]pyrene is a procarcinogen, meaning that the mechanism of carcinogenesis
of benzo[a]pyrene depends on enzymatic metabolism of benzo[a]pyrene to the ultimate mutagen, benzo[a]pyrene diol epoxide, pictured above at right. This molecule intercalates
in DNA
, covalently
bonding to the nucleophilic
guanine
nucleobase
s at the N2 position. X-ray crystallographic
and nuclear magnetic resonance
structure studies show that this binding distorts the DNA, 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.
There are indications that benzo[a]pyrene diol epoxide specifically targets the protective p53
gene. 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
) transversion
s in transversion hotspots within p53
, there is a probability that benzo[a]pyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer.
Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is the carcinogenic product of three enzymatic reactions:
Benzo[a]pyrene induces cytochrome P450
1A1 (CYP1A1) by binding to the AHR (aryl hydrocarbon receptor
) in the cytosol. 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
of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production. This process is similar to induction of CYP1A1 by certain polychlorinated biphenyl
s and dioxins.
Recently, benzo[a]pyrene has been found to activate a transposon, LINE1
, in humans.
Polycyclic aromatic hydrocarbon
Polycyclic aromatic hydrocarbons , also known as poly-aromatic hydrocarbons or polynuclear aromatic hydrocarbons, are potent atmospheric pollutants that consist of fused aromatic rings and do not contain heteroatoms or carry substituents. Naphthalene is the simplest example of a PAH...
whose metabolites are mutagen
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
ic and highly carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
ic. Benzo[a]pyrene is listed as a Group 1 carcinogen by the IARC
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
. It belongs to a class of polycyclic aromatic compounds known as benzopyrene
Benzopyrene
Benzo[a]pyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon whose metabolites are mutagenic and highly carcinogenic. Benzo[a]pyrene is listed as a Group 1 carcinogen by the IARC. It belongs to a class of polycyclic aromatic compounds known as benzopyrenes, which consist of a benzene...
s, which consist of a benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
ring fused to a pyrene
Pyrene
Pyrene is a polycyclic aromatic hydrocarbon consisting of four fused benzene rings, resulting in a flat aromatic system. The chemical formula is . This colourless solid is the smallest peri-fused PAH...
molecule. Benzo[a]pyrene is a product of incomplete combustion
Combustion
Combustion or burning is the sequence of exothermic chemical reactions between a fuel and an oxidant accompanied by the production of heat and conversion of chemical species. The release of heat can result in the production of light in the form of either glowing or a flame...
at temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
s between 300 and 600 °C (572 and 1,112 °F). Benzo[a]pyrene was determined in 1933 to be the component of coal tar
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...
responsible for the first recognized occupation-associated cancers, the sooty warts
Soot wart
Chimney sweep's cancer called Soot wart, is a squamous cell carcinoma of the skin of the scrotum. It has the distinction of being the first reported form of occupational cancer, and was initially identified by Percival Pott in 1775....
(cancers of the scrotum
Scrotum
In some male mammals the scrotum is a dual-chambered protuberance of skin and muscle containing the testicles and divided by a septum. It is an extension of the perineum, and is located between the penis and anus. In humans and some other mammals, the base of the scrotum becomes covered with curly...
) 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, the toxicity of benzo[a]pyrene was demonstrated when malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar
Coal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...
. When the body's metabolism attempts to remove Benzo[a]pyrene by converting into a water soluble compound for easier excretion. The resulting diol epoxide, however, reacts with and binds to DNA resulting in mutations which can lead to cancer.
Sources of Benzo[a]pyrene
Benzo[a]pyrene is found in coal tarCoal tar
Coal tar is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal iscarbonized to make coke or gasified to make coal gas...
, in automobile exhaust fumes
Motor vehicle emissions
Motor vehicle emissions are composed of the by-products that comes out of the exhaust systems or other emissions such as gasoline evaporation...
(especially from diesel engine
Diesel engine
A diesel engine is an internal combustion engine that uses the heat of compression to initiate ignition to burn the fuel, which is injected into the combustion chamber...
s), in all smoke resulting from the combustion of organic material (including cigarette smoke), and in charbroiled food. Recent studies have revealed that levels of benzo[a]pyrene in burnt toast
Toast
Toast is bread that has been browned by exposure to radiant heat. This browning reaction is known as the Maillard reaction. Toasting warms the bread and makes it firmer, so it holds toppings more securely...
are significantly higher than once thought, although it is unproven whether burnt toast is itself carcinogenic. Cooked meat products, regular consumption of which has been epidemiologically associated with increased levels of colon cancer (although this in itself does not prove carcinogenicity), have been shown to contain up to 4 ng/g of benzo[a]pyrene, and up to 5.5 ng/g in fried chicken and 62.6 ng/g in overcooked charcoal barbecued beef.
Toxicity
A vast 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, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion). Researchers at Kansas State UniversityKansas State University
Kansas State University, commonly shortened to K-State, is an institution of higher learning located in Manhattan, Kansas, in the United States...
recently discovered a link between vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
deficiency and emphysema
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
in smokers. Benzo[a]pyrene was found to be behind the link, 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
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
. Benzo[a]pyrene, found in tobacco smoke (including cigarette smoke), was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of most malignant lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
tumours.
A 2001 National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
study found levels of benzo[a]pyrene to be significantly higher in foods that were cooked well-done on the barbecue
Barbecue
Barbecue or barbeque , used chiefly in the United States, Canada, the United Kingdom, New Zealand and Australia is a method and apparatus for cooking meat, poultry and occasionally fish with the heat and hot smoke of a fire, smoking wood, or hot coals of...
, particularly steak
Steak
A steak is a cut of meat . Most are cut perpendicular to the muscle fibers, improving the perceived tenderness of the meat. In North America, steaks are typically served grilled, pan-fried, or broiled. The more tender cuts from the loin and rib are cooked quickly, using dry heat, and served whole...
s, chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
with skin, and hamburger
Hamburger
A hamburger is a sandwich consisting of a cooked patty of ground meat usually placed inside a sliced bread roll...
s. Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
ese scientists showed that cooked beef
Beef
Beef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...
contains mutagens, chemicals that are capable of altering the chemical structure of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. However, the foods themselves are not necessarily carcinogenic, even if they contain trace amounts of carcinogens, because the gastrointestinal tract protects itself against carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
s by shedding its outer layer continuously. Furthermore, detoxification enzymes, such as cytochromes 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 benzo[a]pyrene 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 1A1 (CYP1A1
CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.-Function:...
) and cytochrome P450 1B1 (CYP1B1
CYP1B1
Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.- Function :CYP1B1 belongs to the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids...
) are both protective and, confusingly, necessary for benzo[a]pyrene toxicity. Experiments with strains of mice engineered to remove (knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
) CYP1A1
CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.-Function:...
and CYP1B1
CYP1B1
Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.- Function :CYP1B1 belongs to the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids...
reveal that CYP1A1 primarily acts to protect mammals from low doses of benzo[a]pyrene, and that removing this protection causes the biological accumulation of large concentrations of benzo[a]pyrene. Unless CYP1B1
CYP1B1
Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.- Function :CYP1B1 belongs to the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids...
is also knocked out, benzo[a]pyrene toxicity results from the bioactivation of benzo[a]pyrene to the ultimate toxic compound, benzo[a]pyrene -7,8-dihydrodiol-9,10-epoxide (see below).
Interaction with DNA
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
of benzo[a]pyrene depends on enzymatic metabolism of benzo[a]pyrene to the ultimate mutagen, benzo[a]pyrene diol epoxide, pictured above at right. This molecule intercalates
Intercalation (chemistry)
In chemistry, intercalation is the reversible inclusion of a molecule between two other molecules . Examples include DNA intercalation and graphite intercalation compounds.- DNA intercalation :...
in DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, covalently
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
bonding to the nucleophilic
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
nucleobase
Nucleobase
Nucleobases are a group of nitrogen-based molecules that are required to form nucleotides, the basic building blocks of DNA and RNA. Nucleobases provide the molecular structure necessary for the hydrogen bonding of complementary DNA and RNA strands, and are key components in the formation of stable...
s at the N2 position. X-ray crystallographic
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
and nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
structure studies show that this binding distorts the DNA, 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
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
after exposure. This mechanism of action is similar to that of aflatoxin
Aflatoxin
Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, the most notable ones being Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are toxic and among the most carcinogenic substances known...
which binds to the N7 position of guanine.
There are indications that benzo[a]pyrene diol epoxide specifically targets the protective p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
gene. This gene is a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
that regulates the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
and hence functions as a tumor suppressor. By inducing G (guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
) to T (thymidine
Thymidine
Thymidine is a chemical compound, more precisely a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine in double-stranded DNA...
) transversion
Transversion
In molecular biology, transversion refers to the substitution of a purine for a pyrimidine or vice versa. It can only be reverted by a spontaneous reversion. Because this type of mutation changes the chemical structure dramatically, the consequences of this change tend to be more drastic than those...
s in transversion hotspots within p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, there is a probability that benzo[a]pyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer.
Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is the carcinogenic product of three enzymatic reactions:
-
- Benzo[a]pyrene is first oxidized by cytochrome P450Cytochrome P450 oxidaseThe cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
1A1 to form a variety of products, including (+)benzo[a]pyrene-7,8-epoxide. - This product is metabolized by epoxide hydrolaseEpoxide hydrolaseEpoxide hydrolase functions in detoxication during drug metabolism. It converts epoxides to trans-dihydrodiols, which can be conjugated and excreted from the body. Epoxides result from the degradation of aromatic compounds...
, opening up the epoxideEpoxideAn epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...
ring to yield (-)benzo[a]pyrene-7,8-dihydrodiol. - The ultimate carcinogenCarcinogenA carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
is formed after another reaction with cytochrome P450Cytochrome P450 oxidaseThe cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
1A1 to yield the (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide. It is this diol epoxide that covalently binds to DNA.
- Benzo[a]pyrene is first oxidized by cytochrome P450
Benzo[a]pyrene induces cytochrome P450
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
1A1 (CYP1A1) by binding to the AHR (aryl hydrocarbon receptor
Aryl hydrocarbon receptor
The Aryl hydrocarbon receptor is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones...
) in the cytosol. Upon binding the transformed receptor translocates to the nucleus where it dimerises with ARNT (aryl hydrocarbon receptor nuclear translocator
Aryl hydrocarbon receptor nuclear translocator
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor , and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor,...
) and then binds xenobiotic response elements (XREs) in DNA located upstream of certain genes. This process increases transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production. This process is similar to induction of CYP1A1 by certain polychlorinated biphenyl
Polychlorinated biphenyl
Polychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...
s and dioxins.
Recently, benzo[a]pyrene has been found to activate a transposon, LINE1
Retrotransposon
Retrotransposons are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. They are a subclass of transposon. They are particularly abundant in plants, where they are often a principal component of nuclear DNA...
, in humans.
See also
- BenzopyreneBenzopyreneBenzo[a]pyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon whose metabolites are mutagenic and highly carcinogenic. Benzo[a]pyrene is listed as a Group 1 carcinogen by the IARC. It belongs to a class of polycyclic aromatic compounds known as benzopyrenes, which consist of a benzene...
- Benzo[e]pyreneBenzo(e)pyreneBenzo[e]pyrene is a polycyclic aromatic hydrocarbon with the chemical formula C20H12. It is listed as a Group 3 carcinogen by the IARC.-See also:* Benzopyrene* Benzo[a]pyrene* Benzene* Pyrene, a four-ring analogue...
- PyrenePyrenePyrene is a polycyclic aromatic hydrocarbon consisting of four fused benzene rings, resulting in a flat aromatic system. The chemical formula is . This colourless solid is the smallest peri-fused PAH...
, a four-ring analogue - ToxificationToxificationToxification is the conversion of chemical compounds into more toxic forms. This conversion can take place in the body as well as in substrates such as soil or water...