Comparison of the Mutational Specificities Exhibited by BPDE in Escherichia Coli and CHO Cells

Comparison of the Mutational Specificities Exhibited by BPDE in Escherichia Coli and CHO Cells
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BPDE 在大肠杆菌和 CHO 细胞中表现出的突变特异性的比较

DOI:
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发表时间:
1989
期刊:
影响因子:
--
通讯作者:
B. Glickman
B. Glickman
中科院分区:
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文献类型:
--
作者:
M. Mazur;A. Gordon;C. Bernelot;B. Glickman

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BPDE可能是苯并[a]芘(B[a]P)的最终反应代谢产物,苯并[a]芘是一种众所周知的致癌环境污染物。很明显,大多数化学致癌物只有在代谢成最终致癌和致突变的形式后才会活跃。这些最终致癌物往往是缺乏电子的,因此与DNA中丰富的亲核部位发生反应。已经证实,苯并[a]P是由混合功能加氧酶代谢成多种产物,包括四种对映体形式的BPDE(anti或syn;(+)或(−))(Fahl,1982)。有趣的是,B[a]P在哺乳动物细胞中的代谢主要产生(+)抗BPDE异构体(Yang,et al.,1978)。然而,并不是所有与这些终极致癌物的DNA反应都具有同等的生物学重要性。在CHO细胞的hprt基因座上,BPDE的诱变效率分别为(+)anti-gt;>(−)anti=(+/−)syn,而在TA100细菌的crpt基因座上则显著相反(−)anti=(+/−)syn>(+)anti(Stevens,et al.,1985)。我们还知道,在CD-1和Sencar小鼠中,(+)反对映体的活性是肿瘤启动剂的60倍以上(Pling等人,1984)。
BPDE is presumably the ultimate reactive metabolite of benzo[a]pyrene (B[a]P), a well known carcinogenic environmental pollutant. It has become evident that most chemical carcinogens are active only after metabolism to an ultimate carcinogenic and mutagenic form. These ultimate carcinogens tend to be electron deficient and thus react with nuclephilic sites which are abundant in DNA. It has been established that B[a]P is metabolized by the mixed function oxygenases to a variety of products, including the four enantiomeric forms of BPDE (anti or syn; ( + ) or (−)) (Fahl, 1982). Interestingly, metabolism of B[a]P in mammalian cells produces primarily the (+) anti-BPDE isomer (Yang, et al., 1978). However, not all DNA reactions with these ultimate carcinogens are of equal biological importance. It has been shown at the hprt locus in CHO cells that the respective mutagenic efficiency of BPDE is (+)anti > >(−)anti = (+/−)syn, and remarkably the reverse is seen at the crpt locus in TA100 bacteria (−) anti = (+/−) syn > ( + ) anti (Stevens, et al., 1985). It is also known that the ( + ) anti enantiomer is more than 60 fold more active as a tumor initiator in CD-1 and Sencar mice (Pelling, et al., 1984).
苯并(a)芘抗7,8-二氢二醇9, 10-环氧化物形成苯并(a)芘的动力学和调节膜效应。
DOI: 10.1016/0003-9861(82)90247-8
发表时间: 1982
影响因子: 3.9
作者:
Fahl,WE
通讯作者: Fahl,WE
苯并[a]芘二醇环氧化物:对人类和细菌细胞的不同诱变效率。
DOI: 10.1016/0027-5107(85)90040-5
发表时间: 1985
期刊: Mutation research
影响因子: --
作者:
Stevens,CW;Bouck,N;Burgess,JA;Fahl,WE
通讯作者: Fahl,WE
苯并(a)芘二醇环氧化物诱导的碱敏感损伤占总 DNA 修饰的比例较高。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Sage,E;Haseltine,WA
通讯作者: Haseltine,WA