EFFECTS OF HEPATOCARCINOGENIC INITIATORS ON ALDEHYDE DEHYDROGENASE GENE-EXPRESSION IN CULTURED RAT HEPATIC CELLS

被引:16
作者
HUANG, M [1 ]
LINDAHL, R [1 ]
机构
[1] UNIV S DAKOTA,SCH MED,DEPT BIOCHEM & MOLEC BIOL,VERMILLION,SD 57069
关键词
D O I
10.1093/carcin/11.7.1059
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The effects of certain in vivo inducers of tumor-associated aldehyde dehydrogenase (aldehyde:NAD+ oxidoreductase, EC 1.2.1.3; ALDH) activity on the expression of tumor-associated ALDH (T-ALDH) in vitro have been investigated using cultured rat hepatocytes and hepatoma cell lines. Two distinct groups of T-ALDH inducers have been identified. Three hepatocarcinogenic initiators 2-acetylaminofluorene, diethylnitrosamine and ethionine, which cause changes in T-ALDH in vivo, do not induce T-ALDH activity in cultured rat hepatocytes or hepatoma cell lines following either short-term or long-term exposures. In contrast, polycycic aromatic hydrocarbons, such as 3-methylcholanthrene, benzo[a]pyrene and 7,12-dimethylbenz[a] induce an immediate increase of T-ALDH activity in both cultured rat hepatocytes and hepatoma cell lines. Synthesis and degradation rates of T-ALDH mRNA and protein have also been determined. The synthesis of T-ALDH protein is coupled with the increased synthesis of T-ALDH mRNA when the T-ALDH gene is constitutively expressed or activated by an inducer. Both T-ALDH mRNA (t2-Jan=25-34 h) and protein (t2-Jan=88-95 h) in high T-ALDH activity cell lines or low-activity cell lines treated with an inducer are relatively stable. Combined with previous studies, the results suggest that at least two different mechanisms are involved in T-ALDH gene expression; events occurring during initiation as well as during promotion appear to be involved in the genetically stable changes in T-ALDH gene expression which occur in vivo. The results also indicate that the lack of T-ALDH activity in normal hepatocytes or low-activity hepatoma cell lines is due to repression of the T-ALDH gene rather than to the differential stability of T-ALDH mRNA or protein. © 1990 Oxford University Press.
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页码:1059 / 1065
页数:7
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