BENZO[A]PYRENE DIOL EPOXIDE ADDUCT FORMATION IN MOUSE AND HUMAN HEMOGLOBIN - PHYSICOCHEMICAL BASIS FOR DOSIMETRY

被引：56

作者：

NAYLOR, S ^{[1
]}

GAN, LS ^{[1
]}

DAY, BW ^{[1
]}

PASTORELLI, R ^{[1
]}

SKIPPER, PL ^{[1
]}

TANNENBAUM, SR ^{[1
]}

机构：

[1] MIT,DEPT CHEM,DIV TOXICOL,ROOM 56-309,CAMBRIDGE,MA 02139

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 1990年 / 3卷 / 02期

关键词：

D O I：

10.1021/tx00014a005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The interactions of human hemoglobin (hHb) with the anti-diol epoxide of benzo[a]pyrene (aBaPDE) and with the corresponding tetrols formed by hydrolysis of the epoxide were investigated with the aim of characterizing the covalent adducts formed by reaction of the epoxide with the protein. The major product (80% of the total) was determined to be an ester resulting from oxirane ring opening by one or several (unidentified) carboxylate group(s). Minor products were characterized as adducts formed by reaction with amino or heterocyclic nitrogen by comparison of their UV spectra with those of model compounds. There was no evidence for reaction with cysteine. Formation of ester adducts by aBaPDE with mouse hemoglobin (mHb) following administration of BaP to mice was also investigated. It was found that esters constituted the majority of the adducts formed by aBaPDE and a substantial fraction of the total adducts formed. The esters formed by mHb were significantly less stable than those formed by hHb, both in vivo and in vitro. The instability of mHb ester adducts is believed by be responsible for differences among previous descriptions of the in vivo binding of BaP to mHb. © 1990, American Chemical Society. All rights reserved.

引用

页码：111 / 117

页数：7