ELSEVIER Chemico-Biological Interactions 94 (1995) 73-82 Studies on the effect of sulfite on benzo[a]pyrene-7,8-dihydrodiol activation to reactive intermediates in human polymorphonuclear leukocytes Despina Constantin, Kalika Mehrotra, Alf Wallin, Peter Mold&s, Bengt JernstrGm* Institute of Environmental Medicine, Division of Toxicology, Karolinska Instituter, Box 210, S-17177 Stockholm, Sweden Received 10 June 1993; revision received 11 March 1994; accepted 17 March 1994 Abstract Sodium sulfite, a hydrolysis product of the environmental pollutant sulfur dioxide increased the activation of (-)-truns-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) to the (+)- an&enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,lO-tetrahydrobenzo[a]pyrene (BPDE) in phorbol my&ate acetate (PMA)-stimulated human polymorphonuclear leukocytes (PMNs). This effect was potentiated in the presence of DMSO. No significant effect of sulfite on BP- 7,8-diol activation was observed in resting leukocytes. As revealed by the “P-postlabelling technique the dominant adduct in both intracellular DNA and to DNA added to the leuko- cytes was (+)-anti-BPDE bound to the exocyclic nitrogen of deoxyguanosine. The mechanism underlying the stimulatory effect of sulfite on diol epoxide production and increased DNA- binding probably involves one-electron oxidation of sulfite to a sulfur trioxide radical anion and subsequent reaction with molecular oxygen to form the corresponding peroxyl radical. This step obviously requires PMA-initiated oxidative burst and thus, production of superoxide radical anions (0, Y ). Abbreviations: B[u]P, benzo[a]pyrene; BP-7,8-dial, frans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene; BPDE, rrans-7,8-dihydroxy-9,10-epoxy-7,8,9, lo-tetrahydrobenzo[a]pyrene; DMSO, dimethyl sulfoxide; DlT, dithiothreitol; MPO, myeloperoxidase; PAH, polycyclic aromatic hydrocarbon; PBS, phosphate buffer saline; PEI, polyethyleneimine; PMA, phorbol myristate acetate; PMNs, polymorphonuclear leu- kocytes. * Corresponding author. 0009-2797/95/%09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0009-2797(94)033 IS-3