Effects of pretreatment of male NMRI mice with enzyme inducers or inhibitors on clastogenicity of toluene.

Five groups of young male NMRI mice were pretreated with IP injections of three known inducers of cytochrome P450, Aroclor 1254, phenobarbital and 3-methylcholanthrene, and two inhibitors, metyrapone and alpha-naphthoflavone, 5, 3, 2, 1, and 1 day(s) before receiving toluene, respectively. Toluene was given to animals by IP injections of two similar doses 24 h apart. Increased formation of micronuclei within polychromatic erythrocytes of femoral bone marrow 30 h after the first injection of toluene was recorded. None of the treatments with an inducer or inhibitor alone gave a significant increase in the frequency of micronucleated polychromatic erythrocytes. However, pretreatment of animals with each inducer or even inhibitor resulted in an enhanced clastogenic activity of toluene. Simultaneous injections of an inhibitor and toluene clearly decreased the clastogenicities observed. Enhancement of the clastogenicity of toluene was more evident among Aroclor -pretreated animals than among the other groups. Treatment of animals with a mixture of toluene and benzene did not result in an additive clastogenic activity of benzene. IP injection of a mixture of toluene and every xylene isomer resulted in an enhanced clastogenic activity of toluene, although xylene isomers are not found to be clastogenic.