Publication Date:
2012-01-10
Description:
Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenz[a]anthracene (DMBA) is a model PAH widely used to study tumorigenesis. Mice lacking Langerhans cells (LCs), a signatory epidermal dendritic cell (DC), are protected from cutaneous chemical carcinogenesis, independent of T cell immunity. Investigation of the underlying mechanism revealed that LC-deficient skin was relatively resistant to DMBA-induced DNA damage. LCs efficiently metabolized DMBA to DMBA-trans-3,4-diol, an intermediate proximal to oncogenic Hras mutation, and DMBA-treated LC-deficient skin contained significantly fewer Hras mutations. Moreover, DMBA-trans-3,4-diol application bypassed tumor resistance in LC-deficient mice. Additionally, the genotoxic impact of DMBA on human keratinocytes was significantly increased by prior incubation with human-derived LC. Thus, tissue-associated DC can enhance chemical carcinogenesis via PAH metabolism, highlighting the complex relation between immune cells and carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753811/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753811/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Modi, Badri G -- Neustadter, Jason -- Binda, Elisa -- Lewis, Julia -- Filler, Renata B -- Roberts, Scott J -- Kwong, Bernice Y -- Reddy, Swapna -- Overton, John D -- Galan, Anjela -- Tigelaar, Robert -- Cai, Lining -- Fu, Peter -- Shlomchik, Mark -- Kaplan, Daniel H -- Hayday, Adrian -- Girardi, Michael -- 085780/Wellcome Trust/United Kingdom -- K08 AR002072/AR/NIAMS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 AR056632/AR/NIAMS NIH HHS/ -- R01 CA102703/CA/NCI NIH HHS/ -- R01-AR044077/AR/NIAMS NIH HHS/ -- R01-AR056632/AR/NIAMS NIH HHS/ -- R01CA102703/CA/NCI NIH HHS/ -- T32 AR007016/AR/NIAMS NIH HHS/ -- Cancer Research UK/United Kingdom -- Department of Health/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Jan 6;335(6064):104-8. doi: 10.1126/science.1211600.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22223807" target="_blank"〉PubMed〈/a〉
Keywords:
9,10-Dimethyl-1,2-benzanthracene/*analogs & derivatives/metabolism/toxicity
;
Animals
;
Aryl Hydrocarbon Hydroxylases/metabolism
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Carcinogens/*metabolism/*toxicity
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Carcinoma, Squamous Cell/*chemically induced/metabolism
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Cell Transformation, Neoplastic
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Cells, Cultured
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Cytochrome P-450 CYP1A1/metabolism
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Cytochrome P-450 CYP1B1
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*DNA Damage
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Genes, ras
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Humans
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Keratinocytes/metabolism/pathology
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Langerhans Cells/immunology/*metabolism
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Mice
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Mice, Transgenic
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Skin Neoplasms/*chemically induced/metabolism
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T-Lymphocytes/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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