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诱变致癌物诱导稳定、可遗传的表观遗传变化:一种新的测试系统。

Induction of a stable, heritable epigenetic change by mutagenic carcinogens: a new test system.

作者信息

Toman Z, Dambly C, Radman M

出版信息

IARC Sci Publ. 1980(27):243-55.

PMID:6449480
Abstract

The expression of the E. coli gal operon was set under the direct negative control of phage lambda repressor by a fusion between the gal operon an the active cI cro segment of phage lambda genoma. This system can exist in two stable but reversible epigenetic states: (A) the immune cI+ cro- gal- state (white colonies on McConkey gal plates) and (B) the nonimmune cI- cro+ gal+ state (red colonies). Transcription of this gal operon depends upon activation of the PR promoter; hence requiring the removal of lambda immunity repressor (cI) from the oR operator. Short exposure of this E. coli strain to radiation or chemical mutagens/carcinogens leads to a stable, inherited loss of the cI repressor (due to the take-over by the cro repressor, repressing the cI gene) and subsequent constitutive expression of the gal operon. This switch, from the (A) state to the (B) state, depends upon E. coli recA+ and lambda cro+ genes and is reversible upon supply of lambda cI repressor; this is consistent with the fact that cI and cro proteins are mutual repressors, i.e., only one of them can be expressed at a given time. This E. coli strain provides the easiest, most accurate and sensitive assay for all mutagenic and SOS-inducing agents.

摘要

通过将大肠杆菌半乳糖操纵子与噬菌体λ基因组的活性cI cro片段融合,使大肠杆菌半乳糖操纵子的表达置于噬菌体λ阻遏物的直接负调控之下。该系统可以存在于两种稳定但可逆的表观遗传状态:(A)免疫cI + cro - gal - 状态(在麦康凯半乳糖平板上为白色菌落)和(B)非免疫cI - cro + gal + 状态(红色菌落)。该半乳糖操纵子的转录取决于PR启动子的激活;因此需要从oR操纵子上去除λ免疫阻遏物(cI)。将这种大肠杆菌菌株短时间暴露于辐射或化学诱变剂/致癌物会导致cI阻遏物的稳定、遗传性丧失(由于cro阻遏物接管,抑制cI基因),随后半乳糖操纵子组成型表达。这种从(A)状态到(B)状态的转变取决于大肠杆菌recA + 和λcro + 基因,并且在提供λcI阻遏物时是可逆的;这与cI和cro蛋白是相互阻遏物这一事实一致,即在给定时间只有其中之一能够表达。这种大肠杆菌菌株为所有诱变剂和SOS诱导剂提供了最简单、最准确和最灵敏的检测方法。

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Induction of a stable, heritable epigenetic change by mutagenic carcinogens: a new test system.诱变致癌物诱导稳定、可遗传的表观遗传变化:一种新的测试系统。
IARC Sci Publ. 1980(27):243-55.
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引用本文的文献

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Mechanisms of multistep carcinogenesis and carcinogen risk assessment.多步骤致癌作用机制与致癌物风险评估
Environ Health Perspect. 1993 Apr;100:9-20. doi: 10.1289/ehp.931009.
2
Inductest and spermatest in genetic toxicology testing.遗传毒理学检测中的诱导试验和精子试验。
Arch Toxicol. 1980 Nov;46(1-2):159-69. doi: 10.1007/BF00361254.
3
Lysogenic induction of lambdoid phages in lexA mutants of Escherichia coli.大肠杆菌lexA突变体中类λ噬菌体的溶原诱导
Mol Gen Genet. 1981;184(3):457-9. doi: 10.1007/BF00352522.