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 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 (O2-.).
Constantin
D
D
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Mehrotra
K
K
Wallin
A
A
Moldéus
P
P
Jernström
B
B
D001711:Biotransformation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004101:Dihydroxydihydrobenzopyrenes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D013237:Stereoisomerism; D013447:Sulfites / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D004101:Dihydroxydihydrobenzopyrenes; D011506:Proteins; D017382:Reactive Oxygen Species; D013447:Sulfites; D014316:Tritium; C017228:benzo(a)pyrene 7,8-dihydrodiol; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; C025026:sodium sulfite; D004121:Dimethyl Sulfoxide