PMID: 9651530Jul 4, 1998Paper

Isolation of a novel metabolizing system enriched in phase-II enzymes for short-term genotoxicity bioassays

Mutation Research
M PaoliniG Cantelli-Forti

Abstract

Murine S9 liver fractions isolated from mice fed 7.5 g kg-1 2(3)-tert-Butyl-4-hydroxyanisole (BHA) for 3 weeks were tested to determine: (a) the profile of both phase-I and phase-II xenobiotic metabolizing enzymes; (b) their ability to induce in vitro covalent binding of some precarcinogens to calf thymus DNA; and (c) their activation in a standard genetic toxicology assay. With regard to phase-I pathway, the S9 fraction expressed various cytochrome P-450-(CYP) (classes 1A1, 1A2, 2B1, 2E1, and 3A)-dependent biotransformation enzymes at levels comparable with those present in murine control liver. For post-oxidative enzymes, the S9 expressed high levels of glutathione S-transferases (up to 12-fold increase), glutathione S-epoxide-transferase (up to 2.6-fold), UDP-glucuronosyl transferase (up to 5.3-fold) and epoxide hydrolase (up to 2.6-fold) activities, as compared to untreated mice. The in vitro DNA binding of the precarcinogenic agents [14C]-1,4-dichlorobenzene, [14C]-1,2-dichlorobenzene and [14C]-1,4-dibromobenzene, mediated by BHA-induced cytosol and/or microsomal preparation, showed an increase in specific activity comparable to that observed with phase-I (PB/beta NF) induced S9. In some instances, covalent binding was eve...Continue Reading

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Citations

Jun 6, 2003·Mutation Research·Moreno Paolini, Marion Nestle
Oct 11, 2012·Journal of Biomedicine & Biotechnology·Andrea SaponeMoreno Paolini
Apr 6, 1999·Chemico-biological Interactions·R MundayC M Munday
Dec 16, 1998·Toxicology and Applied Pharmacology·M Paolini
Mar 3, 1999·Regulatory Toxicology and Pharmacology : RTP·J A Barter, J H Sherman
Jan 29, 2000·The Journal of Investigative Dermatology·A A ShvedovaV E Kagan
Nov 9, 2005·The Journal of Veterinary Medical Science·Shigetoshi AisoTaijiro Matsushima

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