Exposure to various benzene derivatives differently induces cytochromes P450 2B1 and P450 2E1 in rat liver

Abstract

Benzene (B), toluene (T), ethylbenzene (EB), styrene (S) and xylene isomers (oX, mX, pX) are important environmental pollutants and B is a proved human carcinogen. Their inhalation by male Wistar rats (4 mg/l, 20 h/day, 4 days) caused cytochrome P450 (P450) induction. The degree of P450 2B1 induction increased and that of 2E1 decreased in the series B, T, EB, S, oX, mX and pX, as estimated by Western blots, while neither solvent was as effective for 2B1 induction as phenobarbital and B was more effective for 2E1 than ethanol. The levels of several other P450s decreased after exposure to these solvents, B being most effective. Exposure to these solvents increased in vitro hepatic microsomal oxidation of B and aniline (AN) (2E1 substrates) 3 to 6-fold, indicating induction of this P450. T oxidation was increased 2 to 4-fold and chlorobenzene (ClB) oxidation 3-fold. Sodium phenobarbital (PB, 80 mg/kg/day, 4 days, i.p.) did not increase ethylmorphine (EM) and benzphetamine (BZP) demethylation (2B1 substrates), neither of the B derivatives did so, and oX decreased it; however, pentoxyresorufin O-dealkylation was well related to the immunochemically detected 2B1 levels in control, PB and B microsomes. PB did not increase B, but increased T and ClB oxidation 2-4 and 3-fold, respectively, indicating possible 2B1 role in their oxidation. B oxidation after various inducers was related to immunochemical 2E1 levels, T and ClB oxidation to both 2B1 and 2E1 and AN oxidation to 2E1 and 1A2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Different in Vitro Metabolism of Paclitaxel and Docetaxel in Humans, Rats, Pigs, and Minipigs

“…The livers from pigs and minipigs were obtained 10 min after electrocution, followed by exsanguination. Microsomes were prepared by differential centrifugation as described previously (Gut et al, 1993). P450 concentration was estimated according to the method of Omura and Sato (1964).…”

Cytochromes P450 in benzene metabolism and involvement of their metabolites and reactive oxygen species in toxicity.

“…Role ofCYP in Benzene Oxidation to Soluble Metabolites and to Products that Bind Covalendy to Proteins and DNA In rats exposed to benzene, CYP2E1 induction resulted in a 5-fold increase in its immunochemical level (10) and increased microsomal benzene oxidation in vitro. Thus, induction resulted in rates of formation of soluble metabolites, DNA adducts, and protein adducts 8,9, and 16 times more rapidly than controls at 1 mM benzene (Table 1).…”

“…The total CYP content in microsomes before and after the incubation was estimated according to the method of Omura and Sato (26). The specific CYP immunochemical levels were those reported as before (10), and in human liver, microsomes were assayed in the same way (4,5,21,27).…”

“…Benzene treatment induces its own metabolism by CYP whereby it is oxidized to phenol, hydroquinone, and other metabolites by CYP2E1 in rat, mouse, and human (3)(4)(5)(6)(7)(8)(9)(10)(11) Abbreviations used: BQ, benzoquinone; CYP, cytochrome P450; DEDTC, diethyldithiocarbamate; DMPO, 5,5-dimethyl-1-pyrroline N-oxide; EDTA, ethyleneiamine-tetraacetic acid; ESR, electron spin resonance; HQ, hydroquinone; *02-, superoxide anion radical; OH' radicals; ROS, reactive oxygen species; NADP(H), nicotinamide-adenine dinucleotide phosphate (reduced); TMP, 2,2,6,6-tetramethyl piperidine.…”

Effect of β‐naphthoflavone and phenobarbital on the nephrotoxicity of chlorotrifluoroethylene and 1,1‐dichloro‐2,2‐difluoroethylene in the rat

“…for 4 days in corn oil (4 ml kg −1 ) (Moorthy et al, 1995) and phenobarbital (80 mg kg −1 day −1 ) was administered i.p. for 4 days in saline solution (2 ml kg −1 ) (Gut et al, 1993). In a preliminary study, the levels of different P450 cytochromes in rats treated with these inducers (β-naphthoflavone and phenobarbital) were measured.…”