MODIFICATIONS OF BENZENE MYELOTOXICITY AND METABOLISM BY PHENOBARBITAL, SKF-525A AND 3-METHYLCHOLANTHRENE

It has recently been suggested that the primary myelotoxic species generated from benzene is not produced directly from the parent compound, but from phenol or an even later metabolite (11). Several compounds that alter the activities of microsomal oxidative and conjugating enzymes were studied for their effects on benzene's myelotoxicity and metabolism. Phenobarbital (PB) protected animals from leucopenia and increased both to total amount of phenol as well as the amount of unconjugated phenol excreted in the urine. SKF-525A had no effect on the leucopenia, whereas it reduced the conversion of benzene to phenol without changing the excretion of unconjugated phenol. 3-Methylcholanthrene also did not prevent the leucopenia, but it did increase the conversion of benzene to phenol and the amount of unconjugated phenol excreted during the first days of the experiment. These data indicate that the early phases of benzene's metabolism may be modulated by the drug pretreatments employed, but myelotoxicity was abated only by PB. We conclude that the marrow effect of benzene is due to a metabolic product other than phenol and, furthermore that the formation of this toxic principle is not strictly dependent on the rate of phenol production. © 1979.