Modifications in the myeloclastogenic effect of benzene in mice with toluene, phenobarbital, 3-methylcholanthrene, Aroclor 1254 and SKF-525A.

Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase analysis. Male and female CD-1 mice were treated with 2 doses of benzene (440 mg/kg) or toluene (860 or 1720 mg/kg) or both 24 h apart, and sacrificed 30 h (or 54 h) after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3-MCA), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when the mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment greatly promoted benzene myeloclastogenicity. Females were consistently more resistant to benzene than males. Dose-response curves in benzene-treated mice were much steeper with 3-MCA induction than without. Chromosomal damage was higher with p.o. than i.p. benzene administration.