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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1998-4-16
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pubmed:abstractText |
Previous studies performed in this laboratory have shown that certain benzo(a)pyrene (BaP) metabolites, such as benzo(a)pyrene-7,8-dihydrodiol (BaP-7,8-diol) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), were more effective in elevating intracellular Ca2+ in normal human peripheral blood mononuclear cell (HPBMC) T and B cells than was BaP. Additionally, it has been shown that the suppression of human T cell mitogenesis produced by polycyclic aromatic hydrocarbons (PAHs) and certain BaP metabolites is reversed by treatment with alpha-naphthoflavone (ANF), a cytochrome P450 1A and 1B inhibitor. ANF also diminishes the elevation in intracellular calcium (Ca2+) produced by BaP in HPBMC. In the present studies, we further defined the relationships between intracellular Ca2+ elevation produced by BaP and two immunotoxic P450-derived metabolites, BaP-7,8-diol and BPDE in the Daudi human B cell line. At 1, 4, and 18 h, both BaP-7,8-diol and BPDE produced a significant rise in intracellular Ca2+. This effect, however, was not observed with BaP or benzo(e)pyrene (BeP), a nonimmunotoxic PAH. To evaluate the potential role of cytochrome P450 metabolism in PAH-induced Ca2+ elevation, Daudi cells were pretreated with ANF for 4 h, followed by treatment with BaP metabolites for 18 h. ANF completely reversed the rise in Ca2+ produced by BaP-7,8-diol, but had no effect on the Ca2+ elevation produced by BPDE. These results suggest that BPDE may be the ultimate P450 metabolite responsible for Ca2+ elevation in human B cells. BaP-7,8-diol and BPDE were found to increase tyrosine phosphorylation in Daudi whole cell lysates and to increase tyrosine phosphorylation of two important Src-related protein tyrosine kinases (PTKs), Lyn and Syk. Inhibition of tyrosine phosphorylation by herbimycin A was found to largely prevent the increase in intracellular Ca2+ produced by BaP-7,8-diol and BPDE, suggesting that Ca2+ elevation is coupled to increased tyrosine phosphorylation in Daudi. BPDE was found to produce a statistically significant increase in tyrosine phosphorylation of Lyn and Syk within 10 min of exposure. Collectively, these data demonstrate that certain P450-derived metabolites of BaP may be responsible for PTK activation and an increase intracellular Ca2+, which may alter antigen receptor signaling in human B cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7,8-Dihydro-7,8-dihydroxybenzo(a)pyr...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoflavones,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydroxydihydrobenzopyrenes,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-naphthoflavone,
http://linkedlifedata.com/resource/pubmed/chemical/benzo(a)pyrene 7,8-dihydrodiol,
http://linkedlifedata.com/resource/pubmed/chemical/herbimycin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0041-008X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
149
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
80-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9512730-7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide,
pubmed-meshheading:9512730-B-Lymphocytes,
pubmed-meshheading:9512730-Benzo(a)pyrene,
pubmed-meshheading:9512730-Benzoflavones,
pubmed-meshheading:9512730-Benzoquinones,
pubmed-meshheading:9512730-Calcium,
pubmed-meshheading:9512730-Cell Line,
pubmed-meshheading:9512730-Cytochrome P-450 Enzyme System,
pubmed-meshheading:9512730-Dihydroxydihydrobenzopyrenes,
pubmed-meshheading:9512730-Humans,
pubmed-meshheading:9512730-Lactams, Macrocyclic,
pubmed-meshheading:9512730-Protein-Tyrosine Kinases,
pubmed-meshheading:9512730-Quinones
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pubmed:year |
1998
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pubmed:articleTitle |
Alterations in human B cell calcium homeostasis by polycyclic aromatic hydrocarbons: possible associations with cytochrome P450 metabolism and increased protein tyrosine phosphorylation.
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pubmed:affiliation |
University of New Mexico College of Pharmacy, Toxicology Program, Albuquerque 87131-1066, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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