Effects of benzene on DNA strand breaks in vivo versus benzene metabolite-induced DNA strand breaks in vitro in mouse bone marrow cells.
Previously, we identified p-benzoquinone (BQ) and 1,2,4-benzenetriol (BT) as toxic metabolites of benzene on the basis of their inhibitory effect on DNA synthesis. In the present study, the capability of benzene and the two metabolites to induce DNA strand breaks was investigated in either the in vivo or the in vitro system by comparing the DNA elution rate on a fine membrane filter at alkaline pH. In the in vitro system were bone marrow cells were reacted with test chemicals for 60 min, both BQ and BT induced a dose-related increase in alkali-labile DNA single-strand breaks (SSBs) of bone marrow cells. However, when glutathione (350 micrograms/ml) was added to the same reaction system, the DNA damaging effect of BQ (24 microM) and BT (24 microM) was blocked by 100 and 53%, respectively. Catalase (130 units/ml) completely blocked the DNA damaging effect of BT, while no protection was afforded with BQ. Consistent with these observations, no induction of alkali-labile DNA SSBs was observed in the in vivo system by an anesthetic dose of benzene (1760 mg/kg, ip or po) at 1, 24, and 36 hr postadministration in both male and female ICR mice. These results suggest that benzene exposure would not induce direct DNA strand breaks in vivo under realistic work-related or accidental exposure conditions and also indicate that caution should be exercised in the interpretation of in vitro data for whole-body toxicity evaluation.
Lee
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Biomedical Science Department, General Motors Research Laboratories, Warren, MI 48090-9055.
Garner
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D000818:Animals; D001554:Benzene / Q000633:toxicity*; D016227:Benzoquinones / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D016227:Benzoquinones; D006873:Hydroquinones; C013038:hydroxyhydroquinone; C004532:quinone; D004247:DNA; D001554:Benzene