Inhibition of rna synthesis by benzene metabolites and their covalent binding to dna in rabbit bone marrow mitochondria in vitro

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Abstract
Mitoplasts from rabbit bone marrow cells in vitro incubated with benzene metabolites showed a concentration‐dependent inhibition of mitochondrial RNA synthesis. The 50% molar inhibitory concentration for each metabolite was determined to be p‐benzoquinone, 2 × 10−6; phenol, 2.5 × 10−5; hydroquinone, 5 × 10−5; catechol, 2 × 10−3; benzene, 1.6 × 10−2. Activated metabolites of radiolabeled benzene covalently bound to mitochondrial DNA in vitro. Labeled deoxynucleosides, enzymatically produced from DNA isolated from mitoplasts prelabeled in DNA with [3H]dGTP and exposed to [14C]benzene in vitro, were chromatographed on a Sephadex LH‐20 column to obtain deoxynucleoside‐adducts. The elution profiles indicated that mtDNA contained seven deoxyguanosine‐adducts. A similar experiment in which the mtDNA was prelabeled with [3H]dATP indicated that two deoxyadenosine‐adducts of mt DNA were formed from benzene in vitro. Tentative identification of several deoxyguanosine‐adducts indicates that p‐benzoquinone, hydroquinone, phenol, and 1,2,4‐benzenetriol produced from benzene form adducts with guanine.