Stimulant effect of nitrite on the activation of benzo[a]pyrene-7,8-dihydrodiol in human polymorphonuclear leucocytes.
Addition of sodium nitrite to human polymorphonuclear leucocytes (PMNs), previously treated with phorbol myristate acetate (PMA), significantly stimulates the activation of (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) to products that covalently bind to extracellular DNA and cellular proteins. The reactive metabolites formed from BP-7,8-diol have been identified as (+)-trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], the ultimate carcinogen of benzo[a]pyrene, and benzo[a]pyrene-7,8-dione (BP-7,8-dione). Isolated myeloperoxidase (MPO) in conjunction with hydrogen peroxide (H(2)O(2)) activates BP-7,8-diol to (+)-anti-BPDE. Addition of nitrite to the MPO/H(2)O(2) system markedly increased the formation of (+)-anti-BPDE. Taken together, the results indicate that the principal pathway for the nitrite-stimulated formation of (+)-anti-BPDE in PMA-activated PMNs involves participation of MPO, whereas alternative pathways seem to be operative in the formation of BP-7,8-dione.
Constantin
D
D
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institute, Box 210, S-17177, Stockholm, Sweden.
Wallin
A
A
Moldéus
P
P
Jernström
B
B