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Titolo:
Hydroxylated benzo[a]pyrene metabolites are responsible for in vitro estrogen receptor-mediated gene expression induced by benzo[a]pyrene, but do notelicit uterotrophic effects in vivo
Autore:
Fertuck, KC; Matthews, JB; Zacharewski, TR;
Indirizzi:
Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA Michigan State Univ E Lansing MI USA 48824 Biol, E Lansing, MI 48824 USA Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA Michigan State Univ E Lansing MI USA 48824 l Ctr, E Lansing, MI 48824 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 2, volume: 59, anno: 2001,
pagine: 231 - 240
SICI:
1096-6080(200102)59:2<231:HBMARF>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYCYCLIC AROMATIC-HYDROCARBONS; BREAST-CANCER CELLS; AH RECEPTOR; CONFORMATIONAL-CHANGES; CYTOSOLIC RECEPTOR; EPITHELIAL-CELLS; BETA; BINDING; MICE; CYTOCHROME-P450;
Keywords:
benzo[a]pyrene; polycyclic aromatic hydrocarbon; metabolism; estrogen receptor; receptor isoform; endocrine disrupter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Zacharewski, TR Michigan State Univ, Dept Biochem, Biochem Bldg, E Lansing, MI 48824 USA Michigan State Univ Biochem Bldg E Lansing MI USA 48824 SA
Citazione:
K.C. Fertuck et al., "Hydroxylated benzo[a]pyrene metabolites are responsible for in vitro estrogen receptor-mediated gene expression induced by benzo[a]pyrene, but do notelicit uterotrophic effects in vivo", TOXICOL SCI, 59(2), 2001, pp. 231-240

Abstract

The estrogenic activities of benzo[a]pyrene (B[a]P) and 10 metabolites (1,3-, 7-, and 9-hydroxy-B[a]P; 4,5-, 7,8-, and 9,10-dihydrodihydroxy-B[a]P; and 1,6-, 3,6-, and 6,12-B[a]P-dione) were investigated, in vitro, B[a]P did not displace tritiated 17 beta -estradiol ([H-3]E2) from either a bacterially expressed fusion protein consisting of glutathione-S-transferase linked to the D, E, and F domains of human ER alpha (GST-hER alpha def), or fromfull-length human ER beta (hER beta) at concentrations as high as 60 muM. However, 10 muM B[a]P demonstrated partial agonist activity in human Ga14-ER alpha def and mouse Ga14-ER beta def reporter gene assays in transiently transfected MCF-7 cells, relative to 10 nM E2. 1-, 3-, 7-, and 9-hydroxy-B[a]P were found to bind to both receptor isoforms, each showing a higher affinity for the P isoform. At 10 muM the four monohydroxylated metabolites were able to induce Ga14-hER alpha def- and Ga14-mER beta def-mediated reporter gene expression to levels 20-100% of that caused by 10 nM E2, suggestingthat these metabolites, and not the parent compound, induced reporter geneexpression following B[a]P treatment of transiently transfected MCF-7 cells. In addition, the effect of B[a]P on two estrogen-inducible end points, uterine weight and lactoferrin mRNA levels, was determined in ovariectomizedDBA/2 and C57BL/6 mice. Neither orally administered B[a]P at doses as highas 10 mg/kg body weight nor subcutaneously injected 3- or 9-hydroxy-B[a]P at doses as high as 20 mg/kg induced effects on uterine wet weight or uterine lactoferrin mRNA levels in either strain. These data suggest that B[a]P metabolites that are estrogenic at high concentrations in vitro do not induce estrogenic effects in the mouse uterus.

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Documento generato il 26/09/20 alle ore 11:28:33