ACTIVATION OF (+/-)-TRANS-7,8-DIHYDROXY-7,8-DIHYDROBENZO[A]PYRENE TO DIOLEPOXIDES BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES OR MYELOPEROXIDASE

被引:58
作者
MALLET, WG
MOSEBROOK, DR
TRUSH, MA
机构
[1] JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV TOXICOL SCI,615 N WOLFE ST,ROOM 7032,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR ENVIRONM HLTH SCI,DEPT ENGN,BALTIMORE,MD 21205
关键词
D O I
10.1093/carcin/12.3.521
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-O-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 myeloperoxidase (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 inhibitor, 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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页码:521 / 524
页数:4
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