Evaluation of cytochrome P450 1 (CYP1) and N-acetyltransferase 1 (NAT1) activities in HaCaT cells: implications for the development of in vitro techniques for predictive testing of contact sensitizers.
Identifieur interne : 000540 ( PubMed/Corpus ); précédent : 000539; suivant : 000541Evaluation of cytochrome P450 1 (CYP1) and N-acetyltransferase 1 (NAT1) activities in HaCaT cells: implications for the development of in vitro techniques for predictive testing of contact sensitizers.
Auteurs : Jutta Bonifas ; Jenny Hennen ; Dorothea Dierolf ; Michaela Kalmes ; Brunhilde BlömekeSource :
- Toxicology in vitro : an international journal published in association with BIBRA [ 1879-3177 ] ; 2010.
English descriptors
- KwdEn :
- 4-Aminobenzoic Acid (metabolism), Acetylation, Allergens (toxicity), Arylamine N-Acetyltransferase (metabolism), Cell Line, Cytochrome P-450 CYP1A1 (metabolism), Cytochrome P-450 Enzyme System (metabolism), Dermatitis, Contact (pathology), Humans, Infant, Newborn, Isoenzymes (metabolism), Keratinocytes (drug effects), Keratinocytes (enzymology), Keratinocytes (pathology), Phenylenediamines (metabolism), Promoter Regions, Genetic (genetics), RNA, Messenger (biosynthesis), RNA, Messenger (genetics), Toxicity Tests (methods).
- MESH :
- chemical , biosynthesis : RNA, Messenger.
- chemical , genetics : RNA, Messenger.
- chemical , metabolism : 4-Aminobenzoic Acid, Arylamine N-Acetyltransferase, Cytochrome P-450 CYP1A1, Cytochrome P-450 Enzyme System, Isoenzymes, Phenylenediamines.
- chemical , toxicity : Allergens.
- drug effects : Keratinocytes.
- enzymology : Keratinocytes.
- genetics : Promoter Regions, Genetic.
- methods : Toxicity Tests.
- pathology : Dermatitis, Contact, Keratinocytes.
- Acetylation, Cell Line, Humans, Infant, Newborn.
Abstract
Xenobiotic metabolizing enzymes like cytochrome P450s and N-acetyltransferase are expressed in keratinocytes and professional antigen-presenting cells. Thus, biotransformation of chemicals applied to the skin can be relevant for their potential to cause skin toxicity and immune responses like allergic contact dermatitis. Considering the keratinocyte cell line HaCaT as a relevant in vitro tool for epidermal biotransformation, we specifically investigated CYP1 (EROD) and N-acetyltransferase 1 (NAT1) activities of three different HaCaT shipments and human primary keratinocytes (NHEK). Solvent treated HaCaT showed EROD levels near the detection limit (0.047 pmol/mg/min), primary keratinocytes (n=4) were in a range between 0 and 0.76 pmol/mg/min. B[a]P (1 microM) induced EROD activities of 19.0+/-0.9 pmol/mg/min (n=11) in HaCaT and 5.8+/-0.5 pmol/mg/min (n=4) in NHEK. N-acetylation activities for para-aminobenzoic acid (PABA) were in average 3.4-fold higher in HaCaT compared to NHEK (8+/-0.5 nmol/mg/min) and varied between the HaCaT shipments (range 12.0-44.5 nmol/mg/min). This was in good agreement with NAT1 promoter P1 dependent mRNA level and N-acetylation of the contact allergen para-phenylenediamine (PPD) under typical cell-based assay conditions. We conclude that HaCaT represent a suitable in vitro model for studying the qualitative contribution of epidermal phase1/phase2 metabolism to toxicological endpoints such as skin sensitization.
DOI: 10.1016/j.tiv.2009.12.023
PubMed: 20036732
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pubmed:20036732Le document en format XML
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last="Kalmes">Michaela Kalmes</name></author><author><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20036732</idno><idno type="pmid">20036732</idno><idno type="doi">10.1016/j.tiv.2009.12.023</idno><idno type="wicri:Area/PubMed/Corpus">000540</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000540</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evaluation of cytochrome P450 1 (CYP1) and N-acetyltransferase 1 (NAT1) activities in HaCaT cells: implications for the development of in vitro techniques for predictive testing of contact sensitizers.</title><author><name sortKey="Bonifas, Jutta" sort="Bonifas, Jutta" uniqKey="Bonifas J" first="Jutta" last="Bonifas">Jutta Bonifas</name><affiliation><nlm:affiliation>Department of Environmental Toxicology, University Trier, Am Wissenschaftspark 25-27, 54296 Trier, Germany. lichter@uni-trier.de</nlm:affiliation></affiliation></author><author><name sortKey="Hennen, Jenny" sort="Hennen, Jenny" uniqKey="Hennen J" first="Jenny" last="Hennen">Jenny Hennen</name></author><author><name sortKey="Dierolf, Dorothea" sort="Dierolf, Dorothea" uniqKey="Dierolf D" first="Dorothea" last="Dierolf">Dorothea Dierolf</name></author><author><name sortKey="Kalmes, Michaela" sort="Kalmes, Michaela" uniqKey="Kalmes M" first="Michaela" last="Kalmes">Michaela Kalmes</name></author><author><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name></author></analytic><series><title level="j">Toxicology in vitro : an international journal published in association with BIBRA</title><idno type="eISSN">1879-3177</idno><imprint><date when="2010" 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Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>4-Aminobenzoic Acid</term><term>Arylamine N-Acetyltransferase</term><term>Cytochrome P-450 CYP1A1</term><term>Cytochrome P-450 Enzyme System</term><term>Isoenzymes</term><term>Phenylenediamines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Allergens</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Keratinocytes</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Keratinocytes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Promoter Regions, Genetic</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Toxicity Tests</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Dermatitis, Contact</term><term>Keratinocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Acetylation</term><term>Cell Line</term><term>Humans</term><term>Infant, Newborn</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Xenobiotic metabolizing enzymes like cytochrome P450s and N-acetyltransferase are expressed in keratinocytes and professional antigen-presenting cells. Thus, biotransformation of chemicals applied to the skin can be relevant for their potential to cause skin toxicity and immune responses like allergic contact dermatitis. Considering the keratinocyte cell line HaCaT as a relevant in vitro tool for epidermal biotransformation, we specifically investigated CYP1 (EROD) and N-acetyltransferase 1 (NAT1) activities of three different HaCaT shipments and human primary keratinocytes (NHEK). Solvent treated HaCaT showed EROD levels near the detection limit (0.047 pmol/mg/min), primary keratinocytes (n=4) were in a range between 0 and 0.76 pmol/mg/min. B[a]P (1 microM) induced EROD activities of 19.0+/-0.9 pmol/mg/min (n=11) in HaCaT and 5.8+/-0.5 pmol/mg/min (n=4) in NHEK. N-acetylation activities for para-aminobenzoic acid (PABA) were in average 3.4-fold higher in HaCaT compared to NHEK (8+/-0.5 nmol/mg/min) and varied between the HaCaT shipments (range 12.0-44.5 nmol/mg/min). This was in good agreement with NAT1 promoter P1 dependent mRNA level and N-acetylation of the contact allergen para-phenylenediamine (PPD) under typical cell-based assay conditions. We conclude that HaCaT represent a suitable in vitro model for studying the qualitative contribution of epidermal phase1/phase2 metabolism to toxicological endpoints such as skin sensitization.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20036732</PMID><DateCreated><Year>2010</Year><Month>03</Month><Day>09</Day></DateCreated><DateCompleted><Year>2010</Year><Month>06</Month><Day>22</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1879-3177</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>3</Issue><PubDate><Year>2010</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Toxicology in vitro : an international journal published in association with BIBRA</Title><ISOAbbreviation>Toxicol In Vitro</ISOAbbreviation></Journal><ArticleTitle>Evaluation of cytochrome P450 1 (CYP1) and N-acetyltransferase 1 (NAT1) activities in HaCaT cells: implications for the development of in vitro techniques for predictive testing of contact sensitizers.</ArticleTitle><Pagination><MedlinePgn>973-80</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.tiv.2009.12.023</ELocationID><Abstract><AbstractText>Xenobiotic metabolizing enzymes like cytochrome P450s and N-acetyltransferase are expressed in keratinocytes and professional antigen-presenting cells. Thus, biotransformation of chemicals applied to the skin can be relevant for their potential to cause skin toxicity and immune responses like allergic contact dermatitis. Considering the keratinocyte cell line HaCaT as a relevant in vitro tool for epidermal biotransformation, we specifically investigated CYP1 (EROD) and N-acetyltransferase 1 (NAT1) activities of three different HaCaT shipments and human primary keratinocytes (NHEK). Solvent treated HaCaT showed EROD levels near the detection limit (0.047 pmol/mg/min), primary keratinocytes (n=4) were in a range between 0 and 0.76 pmol/mg/min. B[a]P (1 microM) induced EROD activities of 19.0+/-0.9 pmol/mg/min (n=11) in HaCaT and 5.8+/-0.5 pmol/mg/min (n=4) in NHEK. N-acetylation activities for para-aminobenzoic acid (PABA) were in average 3.4-fold higher in HaCaT compared to NHEK (8+/-0.5 nmol/mg/min) and varied between the HaCaT shipments (range 12.0-44.5 nmol/mg/min). This was in good agreement with NAT1 promoter P1 dependent mRNA level and N-acetylation of the contact allergen para-phenylenediamine (PPD) under typical cell-based assay conditions. We conclude that HaCaT represent a suitable in vitro model for studying the qualitative contribution of epidermal phase1/phase2 metabolism to toxicological endpoints such as skin sensitization.</AbstractText><CopyrightInformation>Copyright (c) 2010 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bonifas</LastName><ForeName>Jutta</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Environmental Toxicology, University Trier, Am Wissenschaftspark 25-27, 54296 Trier, Germany. lichter@uni-trier.de</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hennen</LastName><ForeName>Jenny</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Dierolf</LastName><ForeName>Dorothea</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Kalmes</LastName><ForeName>Michaela</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Blömeke</LastName><ForeName>Brunhilde</ForeName><Initials>B</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>12</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Toxicol In Vitro</MedlineTA><NlmUniqueID>8712158</NlmUniqueID><ISSNLinking>0887-2333</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000485">Allergens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007527">Isoenzymes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010655">Phenylenediamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>9035-51-2</RegistryNumber><NameOfSubstance UI="D003577">Cytochrome P-450 Enzyme System</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="D019363">Cytochrome P-450 CYP1A1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.5</RegistryNumber><NameOfSubstance UI="D001191">Arylamine N-Acetyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.5</RegistryNumber><NameOfSubstance UI="C089384">N-acetyltransferase 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>TL2TJE8QTX</RegistryNumber><NameOfSubstance UI="D010129">4-Aminobenzoic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D010129" MajorTopicYN="N">4-Aminobenzoic Acid</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000107" MajorTopicYN="N">Acetylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000485" MajorTopicYN="N">Allergens</DescriptorName><QualifierName UI="Q000633" 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MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018675" MajorTopicYN="N">Toxicity Tests</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2009</Year><Month>10</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2009</Year><Month>11</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2009</Year><Month>12</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>12</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>12</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>6</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20036732</ArticleId><ArticleId IdType="pii">S0887-2333(09)00387-7</ArticleId><ArticleId IdType="doi">10.1016/j.tiv.2009.12.023</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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