Trenbolone growth promotant: covalent DNA binding in rat liver and inSalmonella typhimurium, and mutagenicity in the Ames test

DNA-binding of carbamazepine (CBZ) and oxcarbazepine (OCBZ) catalysed by non-induced, phenobarbital-induced or methylcholanthrene-induced rat liver microsomes in vitro was studied. 14C-CBZ 200 nmol incubated with DNA, liver microsomes and cofactors led to the formation of a significant amount of CBZ-epoxide, which has been suspected as the cause of teratogenesis and other side- effects of CBZ,1,2 but has not been reactive in any test systems for genotoxicity, including the Ames test.3 No enzyme-dependent DNA-binding of CBZ was found. Using the same conditions, however, OCBZ was bound to DNA. This binding was dependent on the presence of NADPH. 10-hydroxy-10,11-dihydro-carbamazepine, which is known to be the major metabolite of OCBZ, and an unknown peak were demonstrated by HPLC. These results are the first indication of a higher level of covalent DNA binding of OCBZ than of CBZ. The nature of the unknown metabolite and the pathway leading to covalent binding remain to be studied.

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Identification of a single-stranded DNA binding protein from rat liver with high mobility group protein 1.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)81017-7 ◽

1982 ◽

Vol 257 (6) ◽

pp. 2722-2725

Author(s):

C Bonne ◽

P Sautiere ◽

M Duguet ◽

A M de Recondo

Keyword(s):

Dna Binding ◽

Rat Liver ◽

Binding Protein ◽

High Mobility ◽

Dna Binding Protein ◽

High Mobility Group ◽

High Mobility Group Protein ◽

Single Stranded Dna ◽

Group Protein

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A monoclonal antibody to rat liver cytochrome P450 IIC11 strongly and regiospecifically inhibits constitutive benzo[a]pyrene metabolism and DNA binding

Molecular Carcinogenesis ◽

10.1002/mc.2940040409 ◽

1991 ◽

Vol 4 (4) ◽

pp. 308-314 ◽

Cited By ~ 10

Author(s):

Rosa Todorovic ◽

Prabhaker D. Devanesan ◽

Ercole L. Cavalieri ◽

Eleanor G. Rogan ◽

Sang S. Park ◽

...

Keyword(s):

Monoclonal Antibody ◽

Cytochrome P450 ◽

Dna Binding ◽

Rat Liver ◽

Liver Cytochrome

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Potency of Carcinogens Derived from Covalent DNA Binding and Stimulation of DNA Synthesis in Rat Liver

Toxicologic Pathology ◽

10.1177/019262338401200118 ◽

1984 ◽

Vol 12 (1) ◽

pp. 106-111 ◽

Cited By ~ 7

Author(s):

Werner K. Lutz ◽

Marie-Therese Büsser ◽

Peter Sagelsdorff

Keyword(s):

Dna Binding ◽

Dna Synthesis ◽

Rat Liver ◽

Stimulation Of

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cDNA cloning and expression of rat homeobox gene, Hex, and functional characterization of the protein

Biochemical Journal ◽

10.1042/bj3390111 ◽

1999 ◽

Vol 339 (1) ◽

pp. 111-117 ◽

Cited By ~ 31

Author(s):

Takashi TANAKA ◽

Tetsuya INAZU ◽

Kazuya YAMADA ◽

Zaw MYINT ◽

Vincent W. KENG ◽

...

Keyword(s):

Dna Binding ◽

Binding Site ◽

Rat Liver ◽

Functional Characterization ◽

Homeobox Gene ◽

Hepatoma Cells ◽

Cloning And Expression ◽

Expression Vectors ◽

Luciferase Reporter ◽

Cdna Clones

We isolated two cDNA clones of rat Hex, a homeobox protein, studied its expression in rat liver and various cells, and characterized the protein. The levels of Hex mRNA were only slightly increased in liver of rats refed with a high-carbohydrate diet or after partial hepatectomy. Whereas the expression of Hex mRNA was detected in hepatocytes isolated from adult rat liver and also in highly differentiated hepatoma cells, no Hex mRNA was detected in poorly differentiated hepatoma cells. Hex mRNA was also detected in liver from embryo aged 15 days. Expression of Hex was increased in F9 cells during differentiation into visceral endoderm cells by treatment with retinoic acid. This stimulation occurred prior to an increase in the level of α-fetoprotein mRNA. When fusion-protein expression vectors of GAL4 DNA-binding domain and Hex were co-transfected with luciferase reporter plasmid, with or without five copies of the GAL4-binding site, into HepG2 cells, the luciferase activities were decreased in concentration- and GAL4-binding site-dependent manners. This repression did not require the presence of the homeodomain, which is located between the amino acid residues 137 and 196. Its repression domain was mapped between the residues 45 and 136 in the proline-rich N-terminal region. In addition, the homeodomain was responsible for DNA-binding of Hex. These results indicate that Hex functions as a transcriptional repressor and may be involved in the differentiation and/or maintenance of the differentiated state in hepatocytes.

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