Effect of dimethyl sulfoxide on the genotoxicity and metabolism of benzene in vivo.

The mechanism of the genotoxicity and metabolism of benzene (BZ) was investigated by using a free-radical scavenger, dimethyl sulfoxide (DMSO), to investigate the free radical mechanism in BZ metabolism. The presence of chromosomal breakage expressed as micronuclei (MN) in bone marrow polychromatic erythrocytes (PCE) and the presence of several BZ metabolites in the urine were monitored. Adult male ICR mice were exposed orally to DMSO after oral exposure to BZ (440 mg/kg b.w.). DMSO was administered either in different concentrations (1.25, 3.75 or 12.5% given at a volume of 0.01 ml/gm b.w.) or at different intervals after BZ exposure (1, 3 or 5 h). Each group consisted of five mice. It was found that the BZ-induced MN frequency was reduced by DMSO from 48.8 +/- 5.6 (SEM) to 2.6 +/- 0.7 per 1000 PCE when DMSO (12.5%) was administered at 1 h after BZ exposure (P less than 0.01), to 3.4 +/- 0.8 at 3 h (P less than 0.01) and to 36.2 +/- 12.1 at 5 h (P less than 0.01). The reduction of the clastogenic effect of BZ by DMSO was also dependent upon the DMSO doses. The MN frequency was significantly reduced from 48.8 +/- 5.6 to 29.4 +/- 10.9 with 1.25% DMSO (P less than 0.01) to 20 +/- 7.6 with 3.75% (P less than 0.01) and to 2.6 +/- 0.7 with 12.5% DMSO (P less than 0.01). The presence of different metabolites of BZ such as hydroquinone, catechol, trans-trans muconic acid (MA, the oxidized form of trans-trans muconaldehyde, ttM), and total and conjugated phenol was evaluated in the urine of the exposed mice using HPLC. Among these metabolites, the quantity of MA was found to have the closest positive correlation with the MN frequency (P less than 0.007). Phenol but not the other monitored metabolites was also positively correlated with MN frequency (P less than 0.03). Thus, our data show that the formation of genotoxic metabolites from BZ probably involves hydroxyl radicals and ttM as well as phenol are likely to be responsible for the clastogenic effect of benzene in vivo.