STUDIES ON THE EFFECT OF SULFITE ON BENZO[A]PYRENE-7,8-DIHYDRODIOL ACTIVATION TO REACTIVE INTERMEDIATES IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Sodium sulfite, a hydrolysis product of the environmental pollutant sulfur dioxide increased the activation of (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) to the (+)anti-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) in phorbol myristate 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-32-postlabelling technique the dominant adduct in both intracellular DNA and to DNA added to the leukocytes 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 (O-2(.-)).