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Titolo:
ONTOGENIC DEVELOPMENT OF THE DISTRIBUTION OF CONSTITUTIVE AND 3-METHYLCHOLANTHRENE-INDUCED CYP1A1 AND CYP1A2 IN RABBIT LIVER
Autore:
RICH KJ; FOSTER JR; EDWARDS RJ; DAVIES DS; BOOBIS AR;
Indirizzi:
MRC LABS,TOXICOL UNIT,WOODMANSTERNE RD CARSHALTON SM5 4EF SURREY ENGLAND CENT TOXICOL LAB MACCLESFIELD CHESHIRE ENGLAND ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL LONDON W12 0HS ENGLAND
Titolo Testata:
The Journal of histochemistry and cytochemistry
fascicolo: 6, volume: 41, anno: 1993,
pagine: 915 - 925
SICI:
0022-1554(1993)41:6<915:ODOTDO>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-FETAL LIVER; RAT-LIVER; MONOCLONAL-ANTIBODY; MONOOXYGENASE ACTIVITIES; CYTOCHROME-P-450 ISOZYMES; EXTRAHEPATIC TISSUES; TEMPORAL CONTROL; MESSENGER-RNAS; MOUSE EMBRYOS; LOCALIZATION;
Keywords:
ONTOGENY OF CYP1A; LIVER; MONOCLONAL ANTIBODIES; IMMUNOCYTOCHEMICAL STUDIES; RABBIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
K.J. Rich et al., "ONTOGENIC DEVELOPMENT OF THE DISTRIBUTION OF CONSTITUTIVE AND 3-METHYLCHOLANTHRENE-INDUCED CYP1A1 AND CYP1A2 IN RABBIT LIVER", The Journal of histochemistry and cytochemistry, 41(6), 1993, pp. 915-925

Abstract

We investigated the expression, distribution, and inducibility of 3-methylcholanthrene (MC)-inducible P450 enzymes, CYP1A1 and 1A2, in livers of rabbits at different stages of development, ranging from 4 days before birth (-4 days of age) to adulthood. These enzymes were identified by immunoblotting and immunocytochemistry and quantified by dot-blotting, utilizing previously characterized monoclonal antibodies, 107 and 3/4/2, specific for CYP1A2 and both CYP1A1 and 1A2, respectively, and a polyclonal antibody that recognizes both enzymes. Expression of CYP1A2 is always greater than that of CYP1A1 in livers of untreated rabbits, regardless of age. Moreover, immunocytochemistry showed that CYP1A1 is evenly distributed throughout the liver at all ages, whereas CYP1A2 is highly localized to only a few scattered cells at 1 day before birth. More hepatocytes express this enzyme perinatally. By 6 days of age, expression of CYP1A2 is confined to a narrow band of centrilobular cells, but with increasing age the enzyme is expressed in more hepatocytes until weaning, when all hepatocytes are positive. Although CYP1A1 is induced by MC treatment at most ages, there is no change in its distribution. In contrast, induction of CYP1A2 was shown immunocytochemically to occur in only a limited number of hepatocytes in fetal rabbits. There is a progressive increase with age in the number of hepatocytes that are inducible for CYP1A2. The greatest fold-induction of hepatic CYP1A2 by MC in the rabbit is a 9-11 days of age, when, for MC-treated rabbits, CYP1A2 represents >60% of the total P450 pool. The modulation of enzyme expression caused by MC treatment of fetuses/neonates leads to developmentally advanced livers with respect to P450 and could have a significant impact on the fetal and neonatal toxicity of some foreign compounds. These data demonstrate, for the first time, that the ontogenetic expression and localization of CYP1A1 and 1A2 withinthe liver are differentially regulated at the level of the individualcell.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 07:05:35