Linked Life Data

8149487

Source:http://linkedlifedata.com/resource/pubmed/id/8149487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-5-12
pubmed:abstractText
Cultured human mammary carcinoma (MCF-7) cells exhibited constitutive cytochrome P450-dependent metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) (45-75 pmol/mg microsomal protein). Exposure of the cells to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), which is known to induce CYP1A1, not only resulted in a 30-fold increase in the total microsomal metabolism of DMBA but produced substantial differences in the distribution of DMBA metabolites formed. This suggested that different cytochrome P450 (P450) forms predominated in untreated and induced cells. Comparative studies with TCDD-induced human hepatoblastoma (HepG2) and skin cell carcinoma (SCC-13) cells and also recombinantly expressed human CYP1A1, confirmed that the DMBA-metabolite profile in TCDD-induced MCF-7 cells was that of human CYP1A1. This distribution, however, differed substantially from the regioselectivity of rat CYP1A1 and mouse Cyp1a-1. Rabbit antibodies to rat CYP1A1 completely inhibited the DMBA-metabolizing activity of TCDD-induced MCF-7 cells but had no inhibitory effect on constitutive DMBA metabolism which was, however, completely inhibited by chicken antibodies to the novel P450 in mouse embryo fibroblasts (P450-EF). Anti-P450-EF inhibited only 10% of the DMBA-metabolizing activity in the TCDD-induced MCF-7 cell microsomes. Microsomes from untreated MCF-7 cells expressed a 52 kDa protein that was immunodetectable by rabbit anti-P450-EF and failed to express immunodetectable levels of human CYP1A1. DMBA metabolism, therefore, switches from P450-EF in uninduced microsomes to CYP1A1 in TCDD-induced microsomes. The mobility of the P450-EF-like protein in MCF-7 cells was higher than that of P450-EF from C3H/10T1/2CL8 (10T1/2) cells (55 kDa). The 52 kDa protein from MCF-7 cells was induced approximately 8-fold by TCDD while CYP1A1 immunodetectable protein was increased to much higher levels. The SCC-13 cell line exhibited a similar pattern of expression of a 52 kDa P450-EF-like protein and CYP1A1. HepG2 cells expressed the highest levels of CYP1A1 in response to TCDD without expression of the 52 kDa protein.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
725-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Co-expression of human CYP1A1 and a human analog of cytochrome P450-EF in response to 2,3,7,8-tetrachloro-dibenzo-p-dioxin in the human mammary carcinoma-derived MCF-7 cells.
pubmed:affiliation
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't