Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolites p ‐benzoquinone, muconaldehyde and hydroquinone

Using radio‐iron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that p ‐benzoquinone (BQ) and muconaldehyde (MUC) are potent inhibitors of bone marrow function in female mice. These two benzene metabolites reduced iron uptake at dosages of <5–6 mg kg −1 . The combination of MUC and hydroquinone (HQ) (100 mg kg −1 ) was additive, reducing iron incorporation to an extent that was the sum of the effect of each chemical given alone. The combined effect of MUC and BQ was significantly less than additive, demonstrating antagonism in the response. Multiple regression was used to study the contributions of the components of binary mixtures of the benzene metabolites (METAB). Data obtained from standard curves of METAB and their mixtures are separable in regression analysis. Thus, for zero interaction of METAB, the responses would be simply additive, while positive and negative interaction would indicate synergy and antagonism, respectively. T‐testing of the data resulted in non‐significant values for the mixture MUC+HQ, indicating zero interaction and an additive response. The negative t ‐values obtained for the mixture MUC + BQ, however, indicate negative interaction or an antagonistic response. Since mutually exclusive agents share the same binding sites and occupation of a site by one agent excludes its occupation by another, they cannot interact in producing the effect; combinations of these agents show zero interaction and are simply additive. This suggests that HQ and MUC are mutually exclusive and share the same binding site. Conversely, MUC and BQ are mutually non‐exclusive and this requires the presence of at least two binding sites. These results support the hypothesis that the toxic effects of benzene are produced by several metabolites acting interactively.