Editing Benzo(a)pyrene (section)

=== Carcinogenicity ===
B''a''P's metabolites are [[mutagen]]ic and highly [[carcinogen]]ic, and it is listed as a [[List of IARC Group 1 carcinogens|Group 1 carcinogen]] by the [[International Agency for Research on Cancer|IARC]]. Chemical agents and related occupations, Volume 10, A review of Human Carcinogens, IARC Monographs, Lyon France 2009 <ref>A review of human carcinogens—part F: chemical agents and related occupations</ref>

In June 2016, B''a''P was added as benzo[''def'']chrysene to the [[Registration, Evaluation, Authorisation and Restriction of Chemicals|REACH]] Candidate List of [[Substance of very high concern|Substances of very high concern]] for Authorisation.<ref>{{cite web|last1=European Chemicals Agency|title=ED/21/2016|url=http://echa.europa.eu/documents/10162/4b054c5b-8511-4a30-8ef8-35ab143b4fd0|website=ECHA|access-date=21 June 2016}}</ref>

Numerous studies since the 1970s have documented links between B''a''P and cancers.<ref>{{cite book|chapter-url = https://books.google.com/books?id=Fw_G7Sk382IC&q=Benzo%28a%29pyrene-7%2C8-dihydrodiol-9%2C10-epoxide+cas&pg=PA102|first = W.|last = Kleiböhmer|publisher = [[Elsevier]]|year = 2001|chapter = Polycyclic Aromatic Hydrocarbon (PAH) Metabolites|pages = 99–122|title = Environmental Analysis (Volume 3 of Handbook of Analytical Separations)|isbn = 978-0-08-050576-3}}</ref> It has been more difficult to link cancers to specific B''a''P sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion).<ref>{{cite journal | title=Lung Cancer Risk After Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis | journal=Environmental Health Perspectives | volume=112 | issue=9 | pages=970–978 | pmc=1247189 | year=2004 | last1=Armstrong | first1=B. | last2=Hutchinson | first2=E. | last3=Unwin | first3=J. | last4=Fletcher | first4=T. | pmid=15198916 | doi=10.1289/ehp.6895 }}</ref> A link between [[vitamin A]] deficiency and [[emphysema]] in [[smoking|smokers]] was described in 2005 to be due to B''a''P, which induces vitamin A deficiency in rats.<ref>{{Cite web| title=Benzopyrene and Vitamin A deficiency | work=Researcher links cigarettes, vitamin A and emphysema | url=http://www.tobacco.org/news/171229.html| access-date=March 5, 2005 }}</ref>

A 1996 study provided molecular evidence linking components in [[tobacco smoke]] to [[lung cancer]]. B''a''P was shown to cause genetic damage in lung cells that was identical to the damage observed in the [[DNA]] of most malignant [[lung]] tumours.<ref>{{Cite journal |last1=Denissenko |first1=M. F. |last2=Pao |first2=A. |last3=Tang |first3=M. |last4=Pfeifer |first4=G. P. |date=1996-10-18 |title=Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53 |journal=Science |volume=274 |issue=5286 |pages=430–432 |doi=10.1126/science.274.5286.430 |pmid=8832894|bibcode=1996Sci...274..430D |s2cid=3589066 }}</ref>

Regular consumption of [[cooked meats]] has been epidemiologically associated with increased levels of [[colon cancer]]<ref>{{cite journal | pmid = 12351160 | volume=506–507 | title=Well-done red meat, metabolic phenotypes and colorectal cancer in Hawaii | date=September 2002 | journal=Mutat. Res. | pages=205–14 | last1 = Le Marchand | first1 = L | last2 = Hankin | first2 = JH | last3 = Pierce | first3 = LM | display-authors = etal | doi=10.1016/s0027-5107(02)00167-7}}</ref> (although this in itself does not ''prove'' carcinogenicity),<ref>{{cite journal | last1 = Truswell | first1 = AS | date = Mar 2002 | title = Meat consumption and cancer of the large bowel | journal = European Journal of Clinical Nutrition | volume = 56 | issue = Suppl 1| pages = S19–24 | pmid = 11965518 | doi=10.1038/sj.ejcn.1601349| s2cid = 23886438 | doi-access =  }}</ref>
A 2005 NCI study found an increased risk of [[colorectal adenoma]]s was associated with B''a''P intake, and more strongly with B''a''P intake from all foods.<ref>{{Cite journal |last1=Sinha |first1=Rashmi |last2=Kulldorff |first2=Martin |last3=Gunter |first3=Marc J. |last4=Strickland |first4=Paul |last5=Rothman |first5=Nathaniel |display-authors=3|date=August 2005 |title=Dietary benzo[a]pyrene intake and risk of colorectal adenoma |url=https://aacrjournals.org/cebp/article/14/8/2030/258146/Dietary-Benzo-a-Pyrene-Intake-and-Risk-of |journal=Cancer Epidemiology, Biomarkers & Prevention |volume=14 |issue=8 |pages=2030–2034 |doi=10.1158/1055-9965.EPI-04-0854 |pmid=16103456|s2cid=33819830 |doi-access=free }}</ref> 

The detoxification enzymes cytochrome P450 [[CYP1A1|1A1 (CYP1A1)]] and cytochrome P450 [[CYP1B1|1B1 (CYP1B1)]] are both protective and necessary for benzo[''a'']pyrene toxicity. Experiments with strains of mice engineered to remove ([[gene knockout|knockout]]) CYP1A1 and CYP1B1 reveal that CYP1A1 primarily acts to protect mammals from low doses of B''a''P, and that removing this protection accumulates large concentrations of B''a''P. Unless CYP1B1 is also knocked out, toxicity results from the [[bioactivation]] of B''a''P to benzo[''a'']pyrene -7,8-dihydrodiol-9,10-epoxide, the ultimate toxic compound.<ref>Data presented by [[Daniel W. Nebert]] in research seminars 2007</ref>{{better source|date=July 2016}}