Relationship between the oxidation potential of benzene metabolites and their inhibitory effect on DNA synthesis in L5178YS cells
The effects of benzene and its metabolites on the rate of DNA synthesis were measured in the mouse lymphoma cell line, L5178YS. The direct toxicity of benzene could be distinguished from that of its metabolites since bioactivation of benzene in L5178YS cells was not observed. Cells were exposed to benzene, phenol, catechol, hydroquinone, p-benzoquinone, or 1,2,4-benzenetriol over the range of 1.0 X 10(-7) to 1.0 X 10(-2) M for 30 min, and the rate of DNA synthesis was measured at various times after chemical washout. Cell viability and protein synthesis were determined by trypan blue dye exclusion and (3H)leucine incorporation, respectively. Effects were designated as DNA specific when DNA synthesis was inhibited in the absence of discernible effects on cell membrane integrity and protein synthesis. Concentrations of benzene as high as 1 mM had no effect on DNA synthesis. Comparison of the effects at the maximum nontoxic dose for each compound showed that catechol and hydroquinone were the most effective, inhibiting DNA synthesis by 65%. Phenol, benzoquinone, and benzenetriol inhibited DNA synthesis by approximately 40%. Maximum inhibition was observed 60 min after metabolite washout in each case. Benzoquinone was the most potent inhibitor of DNA synthesis, followed by hydroquinone, benzenetriol, catechol, and phenol with ED50 values of 5 X 10(-6), 1 X 10(-5), 1.8 X 10(-4), 2.5 X 10(-4), and 8.0 X 10(-4), respectively. Cyclic voltammetric experiments were performed on the hydroxylated metabolites of benzene to assess the possible involvement of a redox-type mechanism in their inhibition of DNA synthesis. The ease of oxidation of these metabolites correlated with their ED50 values for inhibition of DNA synthesis (r = 0.997). This suggests that oxidation of phenol or one of its metabolites may be necessary for production of the species involved in inhibition of DNA synthesis.
- Research Organization:
- Case Western Reserve Univ., Cleveland, OH
- OSTI ID:
- 5801723
- Journal Information:
- Mol. Pharmacol.; (United States), Vol. 6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZENE
TOXICITY
BENZOQUINONES
DNA REPLICATION
INHIBITION
PHENOL
PYROCATECHOL
BIOSYNTHESIS
METABOLITES
MICE
OXIDATION
THYMIDINE
TRITIUM COMPOUNDS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
AROMATICS
AZINES
CHEMICAL REACTIONS
DEVELOPERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHENOLS
POLYPHENOLS
PYRIMIDINES
QUINONES
RIBOSIDES
RODENTS
SYNTHESIS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)