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Titolo:
Contrasting effects of acute and chronic dietary exposure to 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) on xenobiotic metabolising enzymes in the male Fischer 344 Rat: implications for chemoprevention studies
Autore:
McPherson, RAC; Tingle, MD; Ferguson, LR;
Indirizzi:
Univ Auckland, Div Pharmacol & Clin Pharmacol, Auckland 1000, New Zealand Univ Auckland Auckland New Zealand 1000 acol, Auckland 1000, New Zealand Univ Auckland, Fac Med & Hlth Sci, Discipline Nutr & Auckland Canc, Soc Res Ctr, Auckland 1000, New Zealand Univ Auckland Auckland New Zealand 1000 Ctr, Auckland 1000, New Zealand
Titolo Testata:
EUROPEAN JOURNAL OF NUTRITION
fascicolo: 1, volume: 40, anno: 2001,
pagine: 39 - 47
SICI:
1436-6207(200102)40:1<39:CEOAAC>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
HETEROCYCLIC AROMATIC-AMINES; GLUTATHIONE S-TRANSFERASES; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE IQ; RESPONSIVE ELEMENTS; GENE-EXPRESSION; HUMAN LIVER; RECEPTOR; DNA; ACTIVATION; INDUCTION;
Keywords:
IQ; bioactivation; chemoprevention;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Tingle, MD Univ Auckland, Div Pharmacol & Clin Pharmacol, Private Bag 92019, Auckland1000, New Zealand Univ Auckland Private Bag 92019 Auckland New Zealand 1000 land
Citazione:
R.A.C. McPherson et al., "Contrasting effects of acute and chronic dietary exposure to 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) on xenobiotic metabolising enzymes in the male Fischer 344 Rat: implications for chemoprevention studies", EUR J NUTR, 40(1), 2001, pp. 39-47

Abstract

Background 2-Amino-3-methyl-imidazo [4,5-f] quinoline (IQ) is a mutagen produced in cooked food. It is commonly present in the human diet and often used as a (pro)carcinogen for chemoprevention studies. Many foodstuffs act as chemo-preventers by altering xenobiotic metabolising enzyme expression infavour of detoxication over bioactivation pathways. However, IQ itself canalso affect enzyme expression, which may be a confounding factor in chemoprevention studies. Aim of study Chronic low dose IQ exposure is intuitivelyclosest to the human dietary situation. The aim was to investigate the effects of chronic dietary exposure to IQ on the expression of enzymes involved in the bioactivation and detoxification of xenobiotics and to compare this with acute exposure, often used in chemoprevention studies. Methods Male Fischer rats received IQ (300 ppm) in the diet (AIN-76) for 52 weeks or were given IQ (20 mg.kg(-1)) orally for 3 days. Animals were killed,livers removed and subcellular fractions prepared. A range of enzymes was selected toallow investigation of several cellular mechanisms. Enzyme expression and activity were determined by Western blotting and the use of selective probesubstrates as appropriate. Results Chronic exposure to IQ led to an increase in phase II detoxifying enzymes. Both the activity and expression of glutathione S-transferase (GST-A1/2) were increased, as were NADPH: Quinone oxidoreductase (NQO), UDP-glucuronosyl transferase (UGT) and beta -glucuronidase activities. There were no statistically significant changes in the potential for bioactivation by three cytochrome P450s. In contrast, acute IQ exposure significantly increased the expression and activity of some cytochrome P450 (CYP1A1 and CYP1A2), UGT and beta -glucuronidase, but significantlydecreased glutathione S-transferase expression and activity. There was a non-significant decrease in NQO but no change in CYP3A2 and CYP2EI activities. Conclusions The changes after acute exposure suggest an interaction through the Ah receptor and xenobiotic response element, modified by the glucocorticoid response element. In contrast, the pattern of effects after chronic exposure suggests activation of the antioxidant response element (ARE). Although the acute model is more practically convenient for short-term chemoprevention screening, the data suggest that an entirely new mechanism is being invoked that completely masks effects of the ARE that occur during chronic exposure. There is a danger that chemopreventive strategies developed using acute models may be misleading, since the mechanism is unlikely to occur during human dietary exposures.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 16:34:09