Abstract
The effects of benzene (71432) metabolites on bone marrow stromal cells were investigated in-vitro. Bone marrow cell suspensions were prepared from male B6C3F1-mice and cultured with hydroquinone (123319), benzoquinone (106514), catechol (120809), phenol (108952), and 1,2,4-benzenetriol (533733) at concentrations from 0.0000015 to formed in the presence of these metabolites was determined and compared with values from untreated stromal cell cultures. Stromal cells exposed to metabolites at these same concentrations were also cultured simultaneously with fresh bone marrow cells in agar to measure the effect on the ability of stromal cells to support growth of granulocyte monocyte colony forming cells. Phenol was only effective at the highest dose, where it caused a 42 to 54 percent reduction in the number of colonies formed. Hydroquinone and benzoquinone had dose related effects. Hydroquinone completely inhibited cell growth at concentrations above 0.0000125mole, and benzoquinone had the same effect at a concentration of 0.00005mol. At a concentration of 0.00005mol catechol decreased colony formation 40 percent, but greater concentrations had similar effects. 1,2,4- Benzenetriol induced a 15 to 35 percent increase in colony formation at a concentration of 0.0000031mol, but further increases in the dose produced colony numbers equal to those for controls. In the simultaneous culture system, stromal cell exposure to hydroquinone and benzoquinone produced dose dependent decreases in granulocyte monocyte colonies. 1,2,4-Benzenetriol and catechol were not effected at lower doses, but at 0.0001mol they reduced granulocyte monocyte colony formation to 45 and 20 percent of control values, respectively. The authors conclude that benzene metabolites are toxic to mouse bone marrow stromal cells in-vitro. Metabolites are toxic in this decreasing order: hydroquinone, benzoquinone, 1,2,4- benzenetriol, catechol, and phenol.