Benzo(a)pyrene

Source: Wikipedia, the free encyclopedia.
The correct title of this article is Benzo[a]pyrene. The substitution of any brackets is due to technical restrictions.
Benzo[a]pyrene
Benzo[a]pyrene


Names
Preferred IUPAC name
Benzo[pqr]tetraphene[1]
Other names
  • Benz[a]pyrene
  • Benzo[a]pyrene
  • 3,4-Benzpyrene
  • 3,4-Benzopyrene
  • 3,4-Benz[a]pyrene
  • 3,4-Benzo[a]pyrene
  • Pentacyclo[10.6.2.02,7.09,19.016,20]icosa-1,3,5,7,9,11,13,15,17,19-decaene[citation needed]
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.000.026 Edit this at Wikidata
EC Number
  • 200-028-5
KEGG
RTECS number
  • DJ3675000
UNII
UN number 3077, 3082
  • InChI=1S/C20H12/c1-2-7-17-15(4-1)12-16-9-8-13-5-3-6-14-10-11-18(17)20(16)19(13)14/h1-12H checkY
    Key: FMMWHPNWAFZXNH-UHFFFAOYSA-N checkY
  • InChI=1/C20H12/c1-2-7-17-15(4-1)12-16-9-8-13-5-3-6-14-10-11-18(17)20(16)19(13)14/h1-12H
    Key: FMMWHPNWAFZXNH-UHFFFAOYAQ
  • c1ccc2c(c1)cc3ccc4cccc5c4c3c2cc5
Properties
C20H12
Molar mass 252.316 g·mol−1
Density 1.24 g/cm3 (25 °C)
Melting point 179[2] °C (354 °F; 452 K)
Boiling point 495 °C (923 °F; 768 K)
0.2 to 6.2 μg/L
-135.7·10−6 cm3/mol
Hazards[3]
GHS labelling:
GHS07: Exclamation markGHS08: Health hazardGHS09: Environmental hazard
Danger
H317, H340, H350, H360, H410
P201, P202, P261, P272, P273, P280, P281, P302+P352, P308+P313, P321, P333+P313, P363, P391, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Benzo[a]pyrene (BaP or B[a]P) is a

Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma
, was already known to be connected to soot.

Description

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in coal tar with the formula C20H12. The compound is one of the benzopyrenes, formed by a benzene ring fused to pyrene, and is the result of incomplete combustion at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F).

Sources

The main source of atmospheric BaP is residential wood burning.

charbroiled
food. A 2001 National Cancer Institute study found levels of BaP to be significantly higher in foods that were cooked well-done on the barbecue, particularly steaks, chicken with skin, and hamburgers: Cooked meat products have been shown to contain up to 4 ng/g of BaP,[5] and up to 5.5 ng/g in fried chicken[6] and 62.6 ng/g in overcooked charcoal barbecued beef.[7]

BaP is discharged in wastewater by industries such as

iron and steel mills[8] and aluminium smelters.[9]

History

In the 18th century, young British

chemical mixture to cancer formation. Frequent skin cancers were noted among fuel industry workers in the 19th century. In 1933, BaP was determined to be the compound responsible for these cases, and its carcinogenicity was demonstrated when skin tumors occurred in laboratory animals repeatedly painted with coal tar.[11] BaP has since been identified as a prime carcinogen in cigarette smoke.[12]

Toxicity

Benzo[a]pyrene, showing the base pyrene ring and numbering and ring fusion locations according to IUPAC nomenclature of organic chemistry.

Nervous system

NR2B receptor subunit.[13]

Immune system

BaP has an effect on the number of

IgG and turn the white blood cell into a macrophage. Therefore, macrophage membranes become susceptible to bacterial infections.[14]

Reproductive system

In experiments with male rats, subchronic exposure to inhaled BaP has been shown to generally reduce the function of testicles and epididymis with lower sex steroid/testosterone production and sperm production.[15]

Carcinogenicity

BaP's metabolites are

Group 1 carcinogen by the IARC. Chemical agents and related occupations, Volume 10, A review of Human Carcinogens, IARC Monographs, Lyon France 2009 [16]

In June 2016, BaP was added as benzo[def]chrysene to the REACH Candidate List of Substances of very high concern for Authorisation.[17]

Numerous studies since the 1970s have documented links between BaP and cancers.[18] It has been more difficult to link cancers to specific BaP sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion).[19] A link between vitamin A deficiency and emphysema in smokers was described in 2005 to be due to BaP, which induces vitamin A deficiency in rats.[20]

A 1996 study provided molecular evidence linking components in tobacco smoke to lung cancer. BaP was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA of most malignant lung tumours.[21]

Regular consumption of

colon cancer[22] (although this in itself does not prove carcinogenicity),[23]
A 2005 NCI study found an increased risk of colorectal adenomas was associated with BaP intake, and more strongly with BaP intake from all foods.[24]

The detoxification enzymes cytochrome P450

better source needed
]

Interaction with DNA

carcinogenic
benzo[a]pyren-7,8-dihydrodiol-9,10-epoxide.
A DNA adduct (at center) of benzo[a]pyrene, the major mutagen in tobacco smoke.[26]

Properly speaking, BaP is a

procarcinogen, meaning that its mechanism of carcinogenesis depends on its enzymatic metabolism to BaP diol epoxide[27] It intercalates in DNA, and the electrophilic epoxide is attacked by nucleophilic guanine bases, forming a bulky guanine adduct.[27]
DG rxn with BPDE

X-ray crystallographic and nuclear magnetic resonance structure studies have shown how this binding distorts the DNA[28] by confusing the double-helical DNA structure. This disrupts the normal process of copying DNA and causes 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.[29]

There are indications that benzo[a]pyrene diol epoxide specifically targets the protective

tumor suppressor. By inducing G (guanine) to T (thymidine) transversions 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:[31]

  1. Benzo[a]pyrene is first oxidized by
    1A1 to form a variety of products, including (+)benzo[a]pyrene-7,8-epoxide.[32]
  2. This product is metabolized by epoxide hydrolase, opening up the epoxide ring to yield (−)benzo[a]pyrene-7,8-dihydrodiol.
  3. The ultimate carcinogen is formed after another reaction with
    cytochrome P450
    1A1 to yield the (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide. It is this diol epoxide that covalently binds to DNA.

BaP induces cytochrome P450 1A1 (CYP1A1) by binding to the AHR (

TLR2),[35] which is a eukaryotic receptor for bacterial surface structures such as lipoteichoic acid
.

Moreover, BaP has been found to activate a transposon, LINE1, in humans.[36]

Nucleotide excision repair

As illustrated above, (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) forms bulky covalent DNA adducts with guanines. Most of these adducts can be efficiently eliminated from DNA by the process of nucleotide excision repair.[37] Those adducts that are not removed can cause errors during DNA replication leading to carcinogenic mutations.

See also

References

  1. ISBN 978-0-85404-182-4
    .
  2. ISBN 978-1-4987-5429-3
    .
  3. ^ "benzo[a]pyrene". pubchem.ncbi.nlm.nih.gov.
  4. ^ "Assessment of Benzo-alpha-pyrene Emissions in the Great Lakes Region" (PDF). pp. 23–24.
  5. PMID 11313108
    .
  6. S2CID 21302834
    .
  7. S2CID 35095622
    .
  8. ^ U.S. Environmental Protection Agency (EPA), Washington, D.C. (2002). "Iron and Steel Manufacturing Point Source Category." Code of Federal Regulations, 40 CFR Part 420.
  9. ^ EPA (1984). "Nonferrous Metals Manufacturing Point Source Category." Code of Federal Regulations, 40 CFR Part 421.
  10. ^ Pott, Percivall (1775). Chirurgical Observations …. London, England: L. Hawes, W. Clarke, and R. Collins. pp. 63–68. From p. 67: "The disease, in these people [i.e., chimney sweeps], seems to derive its origin from a lodgment of soot in the rugae of the scrotum, … "
  11. doi:10.1039/jr9330000395
    .
  12. PMID 10413421
    .
  13. PMID 18761371
    ..
  14. PMID 26765097
    .
  15. PMID 18499416.{{cite journal}}: CS1 maint: numeric names: authors list (link
    )
  16. ^ A review of human carcinogens—part F: chemical agents and related occupations
  17. ^ European Chemicals Agency. "ED/21/2016". ECHA. Retrieved 21 June 2016.
  18. ISBN 978-0-08-050576-3
    .
  19. PMID 15198916
    .
  20. ^ "Benzopyrene and Vitamin A deficiency". Researcher links cigarettes, vitamin A and emphysema. Retrieved March 5, 2005.
  21. S2CID 3589066
    .
  22. PMID 12351160
    .
  23. S2CID 23886438
    .
  24. S2CID 33819830
    .
  25. ^ Data presented by Daniel W. Nebert in research seminars 2007
  26. ^ Created from PDB 1JDG Archived 2008-09-22 at the Wayback Machine
  27. ^
    ProQuest 302781013. Retrieved May 9, 2021. {{cite book}}: |work= ignored (help
    )
  28. PMID 12578353
    .
  29. PMID 8042848
    .
  30. S2CID 6134471
    .
  31. PMID 17702526
    .
  32. PMID 8961944
    .
  33. ^
    PMID 10331078
    .
  34. PMID 17997381
    .
  35. PMID 22442665
    .
  36. PMID 16510580
    .
  37. PMID 28607059
    .

External links


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