TY - JOUR
T1 - Activation of (±)-trans-7, 8-dihydroxy-7, 8-dihydrobenzo[apyrene to diolepoxides by human polymorphonuclear leukocytes or myeloperoxidase
AU - Mallet, William G.
AU - Mosebrook, D. Randolph
AU - Trush, Michael A.
N1 - Funding Information:
We thank Ms Patricia Egner for her critical comments and advice regarding HPLC. This research was supported by NIEHS 03760 and American Cancer Society SIC-3. Support from NIEHS Center Grant (ES 03819) is gratefully acknowledged.
PY - 1991/3
Y1 - 1991/3
N2 - Previous studies have demonstrated that the interaction of (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene [(±)-B[a]P-7,8-diol] with 12-0-tetradecanoylphorbol-13-acetate (TPA)-stimulated human polymorphonuclear leukocytes (PMNs) elicited genotoxic effects in bacteria and mammalian cells. Structure-activity studies with various polycyclic aromatic hydrocarbon derivatives suggest that a diolepoxide intermediate(s) was being formed from this chemical-cell interaction. In this study, we demonstrate by stereochemical analysis of tetraol products that primarily anti-diolepoxides are being formed from (±)-B[a]P-7,8-diol by TPA-stimulated PMNs with an anti/syn ratio of 6. Likewise, a myeloperoxidse (MPO)-H2O2 system generated primarily anti-diolepoxides of B[a]P-7,8-diol with an anti/syn ratio > 5. Such ratios are indicative of the epoxidation of B[a]P-7,8-diol via a peroxyl radical or a ferryl oxygen transfer-mediated reaction. Addition of azide, an MPO inibitor, resulted in decreased tetraols from B[a]P-7,8-diol by PMNs or the MPO system. These studies further support the concept that the activation of B[a]P-7,8-diol by PMNs could create a highly localized genotoxic environment which could impact on human health.
AB - Previous studies have demonstrated that the interaction of (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene [(±)-B[a]P-7,8-diol] with 12-0-tetradecanoylphorbol-13-acetate (TPA)-stimulated human polymorphonuclear leukocytes (PMNs) elicited genotoxic effects in bacteria and mammalian cells. Structure-activity studies with various polycyclic aromatic hydrocarbon derivatives suggest that a diolepoxide intermediate(s) was being formed from this chemical-cell interaction. In this study, we demonstrate by stereochemical analysis of tetraol products that primarily anti-diolepoxides are being formed from (±)-B[a]P-7,8-diol by TPA-stimulated PMNs with an anti/syn ratio of 6. Likewise, a myeloperoxidse (MPO)-H2O2 system generated primarily anti-diolepoxides of B[a]P-7,8-diol with an anti/syn ratio > 5. Such ratios are indicative of the epoxidation of B[a]P-7,8-diol via a peroxyl radical or a ferryl oxygen transfer-mediated reaction. Addition of azide, an MPO inibitor, resulted in decreased tetraols from B[a]P-7,8-diol by PMNs or the MPO system. These studies further support the concept that the activation of B[a]P-7,8-diol by PMNs could create a highly localized genotoxic environment which could impact on human health.
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U2 - 10.1093/carcin/12.3.521
DO - 10.1093/carcin/12.3.521
M3 - Article
C2 - 1849053
AN - SCOPUS:0025922974
SN - 0143-3334
VL - 12
SP - 521
EP - 524
JO - Carcinogenesis
JF - Carcinogenesis
IS - 3
ER -