Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Expression cloning for arsenite-resistance resulted in isolation of tumor-suppressor fau cDNA: possible involvement of the ubiquitin system in arsenic carcinogenesis.

Authors: Rossman, T G; Wang, Z

Published In Carcinogenesis, (1999 Feb)

Abstract: Arsenic is a human carcinogen whose mechanism of action is unknown. Previously, this laboratory demonstrated that arsenite acts as a comutagen by interfering with DNA repair, although a specific DNA repair enzyme sensitive to arsenite has not been identified. A number of stable arsenite-sensitive and arsenite-resistant sublines of Chinese hamster V79 cells have now been isolated. In order to gain understanding of possible targets for arsenite's action, one arsenite-resistant subline, As/R28A, was chosen as a donor for a cDNA expression library. The library from arsenite-induced As/R28A cells was transfected into arsenite-sensitive As/S5 cells, and transfectants were selected for arsenite-resistance. Two cDNAs, asr1 and asr2, which confer arsenite resistance to arsenite-hypersensitive As/S5 cells as well as to wild-type cells, were isolated. asr1 shows almost complete homology with the rat fau gene, a tumor suppressor gene which contains a ubiquitin-like region fused to S30 ribosomal protein. Arsenite was previously shown to inhibit ubiquitin-dependent proteolysis. These results suggest that the tumor suppressor fau gene product or some other aspect of the ubiquitin system may be a target for arsenic toxicity and that disruption of the ubiquitin system may contribute to the genotoxicity and carcinogenicity of arsenite.

PubMed ID: 10069470 Exiting the NIEHS site

MeSH Terms: Amino Acid Sequence; Animals; Arsenite Transporting ATPases; Arsenites/toxicity*; Base Sequence; Cells, Cultured/drug effects; Cricetinae; Cricetulus; DNA, Complementary/genetics; DNA, Complementary/isolation & purification*; Drug Resistance/genetics; Genes, Tumor Suppressor; Molecular Sequence Data; Rats; Ribosomal Proteins/genetics; Ribosomal Proteins/isolation & purification*; Teratogens/toxicity*; Transfection

Back
to Top