当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Metallothionein-I and -II knock-out mice are sensitive to cadmium-induced liver mRNA expression of c-jun and p53.

Metallothionein-I and -II knock-out mice are sensitive to cadmium-induced liver mRNA expression of c-jun and p53.

Abstract：

:Zinc pretreatment has been shown in vitro (rat myoblasts) to induce metallothionein (MT) and inhibit cadmium (Cd)-induced protooncogenes c-myc and c-jun mRNA levels. therefore, the purpose of this study was to determine whether the mRNA expression of the protooncogene c-jun as well as the tumor suppressor gene p53 is increased by Cd in the intact animal and, more specifically, in the target organ for Cd toxicity, the liver. Additionally, modulation of the expression of these genes was investigated in the absence of MT. The effect of CdCl2 on the mRNA levels of c-jun and p53 was studied in livers of C57BL/6J (control) and MT-null mice by Northern- and slot-blot analyses. The mRNA for c-jun and p53 were increased by Cd in a dose-dependent fashion. In the control mice, Cd induced c-jun mRNA (5-fold) at 3 and 12 hr and p53 mRNA (1.8- to 2-fold) at 6 and 12 hr. Compared to controls, the MT-null mice were more sensitive to the Cd-induced gene expression. The magnitude of the inductions was more pronounced and the elevated mRNA levels of c-jun and p53 were seen at lower doses of Cd (10mumol/kg in MT-null mice vs 40 mmol/kg in control mice). In conclusion, these data demonstrate that Cd induces mRNA expression of the protooncogene c-jun and tumor suppressor gene p53 in liver, and that MT modulates this effect.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Zheng H,Liu J,Choo KH,Michalska AE,Klaassen CD

doi

10.1006/taap.1996.0029

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

229-35

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041008X96900290

journal_volume

136

pub_type

杂志文章

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