Studies on the effect of sulfite on benzo[ a]pyrene-7,8-dihydrodiol activation to reactive intermediates in human polymorphonuclear leukocytes

Abstract

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 BP7,8-diol activation was observed in resting leukocytes. As revealed by the 32P-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⨪).