PEROXIDASE ACTIVATION OF HYDROQUINONE RESULTS IN THE FORMATION OF DNA-ADDUCTS IN HL-60 CELLS, MOUSE BONE-MARROW MACROPHAGES AND HUMAN BONE-MARROW

Metabolism of benzene results in the formation of multiple metabolites , including hydroquinone (HQ). HQ is a reducing co-substrate for perox idase enzymes, and the resultant semiquinone and para-benzoquinone (p- BQ) may bind to DNA. The role of peroxidase activation in the formatio n of DNA adducts by benzene metabolites has not been established. In t his study we investigated the role of peroxidase activation in the for mation of DNA adducts by HQ and p-BQ in HL-60 cells, human bone marrow (HBM) cells, mouse bone marrow macrophages (MBMM) and the U-937 and R aji leukemia cell lines. Adduct formation was measured by P1-enhanced P-32-postlabeling; peroxidase activity was measured with a spectrophot ometric assay. Treatment with p-BQ resulted in the formation of two DN A adducts in all of the cell fines. The DNA adducts were identical in all of the cells, however, the adduct level varied by 80-fold. Treatme nt with HQ produced one DNA adduct in HL-60 cells, HBM and MBMM; no ad ducts were detected in U-937 or Raji cells. The HQ-DNA adducts in the three cell lines were identical. The adduct level was highest in the H L-60 cells, followed by HBM and MBMM. There was a statistically signif icant correlation between peroxidase activity and the formation of HQ- DNA adducts. These results suggest that peroxidase-mediated metabolism is involved in the activation of HQ to form DNA adducts in mouse bone marrow and HBM.