Comparison of the Metabolism of Benzene and Its Metabolite Phenol in Rat Liver Microsomes

  • Susan K. Gilmour
  • George F. Kalf
  • Robert Snyder
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


It has been known for many years that chronic exposure to benzene leads to bone marrow depression and aplastic anemia and in recent years it has become apparent that benzene can also be leukemogenic (Snyder, 1984). Benzene-induced bone marrow depression is caused by one or more metabolites of benzene (Snyder, et al., 1981). Cytochrane P-450 mediates the first step in benzene metabolism (Gonasun et al., 1973). The initial metabolite formed in the liver is thought to be benzene oxide (Jerina and Daly, 1974) which rearranges to form phenol. Johansson and Ingelmann-Sundberg (1983) suggested that benzene hydroxylation may occur as a result of hydroxyl radical formation during the partially uncoupled mixed function oxidase-mediated metabolism of benzene in which hydrogen peroxide is generated. Nevertheless, it is clear that the major metabolite of benzene., in vivo (Parke and Williams, 1953) and in vitro (Gonasun et al., 1973) is phenol. Because phenol, can be further hydroxylated it is both a product and a substrate in this system. The metabolism of a substrate, either in vivo or in vitro is in part controlled by the concentration at which it encounters the enzyme. In the metabolism of xenoblotic compounds another controlling factor is the type of cytochrome P-450 which metabolizes the compound and hence the importance of enzyme induction. The concentration of an intermediary metabolite such as phenol is a product of the rate at which it is produced and the rate of further metabolism. The issue can be further complicated if both the initial substrate and its metabolite undergo similar reactions and the two compete at the active site of the enzyme. Given this model, we report on some aspects of the metabolism of benzene and phenol.


Double Reciprocal Plot Microsomal Oxidation Hepatic Microsomal Cytochrome Benzene Metabolite Rabbit Bone Marrow 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Susan K. Gilmour
    • 1
  • George F. Kalf
    • 2
  • Robert Snyder
    • 1
  1. 1.Joint Graduate Program in Toxicology RutgersThe State University of New Jersey and the University of Medicine and Dentistry of New Jersey/ Rutgers Medical SchoolPiscatawayUSA
  2. 2.Department of Biochemistry Jefferson Medical CollegeThomas Jefferson UniversityPhiladelphiaUSA

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