EXPOSURE TO VARIOUS BENZENE-DERIVATIVES DIFFERENTLY INDUCES CYTOCHROMES P450-2B1 AND P450-2E1 IN RAT-LIVER

Benzene (B), toluene (T), ethylbenzene (EB), styrene (S) and xylene is omers (oX, mX, pX) are important environmental pollutants and B is a p roved 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 serie s B, T, EB, S, ox, mX and pX, as estimated by Western blots, while nei ther 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 effecti ve. Exposure to these solvents increased in vitro hepatic microsomal o xidation of B and aniline (AN) (2E1 substrates) 3 to 6-fold, indicatin g induction of this P450. T oxidation was increased 2 to 4-fold and ch lorobenzene (CIB) oxidation 3-fold. Sodium phenobarbital (PB, 80 mg/kg /day, 4 days, i.p.) did not increase ethylmorphine (EM) and benzphetam ine (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 contr ol, PB and B microsomes. PB did not increase B, but increased T and C1 B 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 C1B oxidation to both 2B1 and 2E1 an d AN oxidation to 2E1 and 1A2 levels. Very efficient B oxidation by 2E 1 at low B levels indicates that induction of 2E1 may contribute to B myelotoxicity in vivo more than any other P450 enzyme tested, especial ly considering the fact that B is the most efficient inducer of its me tabolism.