Spontaneous and 5-azacytidine-induced reexpression of ornithine carbamoyl transferase in hepatoma cells.

Delers, A; Szpirer, J; Szpirer, C; Saggioro, D

doi:10.1128/mcb.4.4.809

Cited by 24 publications

(11 citation statements)

References 29 publications

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“…Widman et al (1979) observed that rat hepatocyte-hepatoma cell hybrids had 6-10% of the OCT activity of rat liver extract. Delers et al (1984) also observed that variant cells obtained from H4-II-EC3 possessed not more than 7.5% of the OCT activity of normal hepatocytes when they were cultured in a medium in which arginine was replaced by ornithine. This level of OCT activity may be sufficient to sustain the continuous growth of the cells in an arginine-free, ornithine-supplemented medium.…”

Section: Discussionmentioning

confidence: 83%

“…Farmer and Goss (1991) postulated that some activator for the OTC expression was lacking in the hepatoma cells. Delers et al (1984) found that 5-azacytidine treatment induced the OCT expression in the rat hepatoma cells and suggested that hypermethylation was important for this induction. Nishiyori et al (1994) showed the hepatocyte nuclear factor-4 and CCAAT/enhancer binding protein were necessary for the specific expression of this gene in the liver.…”

Section: Discussionmentioning

confidence: 97%

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Expression of ornithine carbamoyltransferase gene in rat hepatoma-derived cell lines, H4-II-E and R-Y121B

et al. 1997

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Summary.The rat R-Y121B cell line is a unique cell line which has ornithine carbamoyltransferase (OCT, EC 2.1.3.3) and can be continuously cultured in a serum-flee medium which lacks arginine but is supplemented with ornithine. The OCT gene expression was examined in R-Y121B cells and their parental H4-II-E cells. OCT activity in R-Y121B cells was about onetenth of that of the adult rat liver while it was not detected at all in H4-II-E cells. Southern hybridization using an OCT cDNA probe containing the entire coding region showed that the OCT gene structure was apparently not different in R-Y121B cells, H4-II-E cells, or rat liver cells. Northern hybridization using the OCT cDNA probe detected a hybridizing signal in R-Y121B cells but not in H4-II-E cells. Reverse transcription-polymerase chain reaction (RT-PCR) showed that an expected size of the OCT cDNA fragment was amplified in R-Y121B cells but not in H4-II-E cells. The amplified fragment was confirmed to be a real rat OCT cDNA by the digestion of this fragment with two restriction enzymes and by the nucleotide sequencing of the fragment. These results indicated that OCT mRNA was present in R-Y121B cells but not in H4-II-E cells. Amino acid analysis showed that arginine was not present in the culture medium but was present in the hydrolysate of R-Y121B cells. The present experiments indicate that transcription, translation, and processing of OCT proceeds normally and the resultant OCT functions in R-Y121B cells, whereas the transcription does not occur in parental H4-II-E cells even though these cells have the normal gene.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 97%

Expression of ornithine carbamoyltransferase gene in rat hepatoma-derived cell lines, H4-II-E and R-Y121B

et al. 1997

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“…OCT is highly expressed in liver and small intestine, and catabolizes the conversion of ornithine to citrulline (Raijman, 1974). However, OCT expression in cancer and other normal tissues is mostly down-regulated due to epigenetic changes such as DNA hypermethylation (Delers et al, 1984).…”

Section: Recombinant Human Arginase (Rharg)mentioning

confidence: 99%

Arginine enzymatic deprivation and diet restriction for cancer treatment

Zam

2017

Braz. J. Pharm. Sci.

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Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo-and radio-therapeutic approaches to be co-applied.

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“…A well known inhibitor of DNA methylation, 5-azacytidine (5-AzaC), is a useful tool for assessing the role of this type of epigenetic phenomenon in cancer, because several studies have shown that the agent is not demonstrably mutagenic in eukaryotic cells (Delers et al, 1984;Kerbel et al, 1984;Landolph & Jones, 1982). The drug is capable of direct transformation of cultured cells (Benedict et al, 1977;Harrison et al, 1983;Hsiao et al, 1985), but the mechanism of action is not clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Drug-induced revertants of adenovirus-transformed cells: retransformation by 5-azacytidine without reactivation of E1a

Weber

Sircar²,

Fleurent³

et al. 1990

Journal of General Virology

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We have isolated drug-resistant variants from adenovirus-transformed rat cells that had concomitantly lost their transformed phenotype. Our aim was to determine the reason for reversion, to attempt retransformation with 5-azacytidine (5-AzaC) and to study the mechanism of retransformation. Of the three cell lines studied, one (G4F) had lost the integrated Ela genes, whereas the other two (G2a and G5) failed to synthesize Ela RNA or proteins. Incubation of these cell lines with 3 ~tM-5-AzaC for 2 days, followed by passaging in the absence of drug, gave rise to transformed foci in all of the cell lines. The efficiency of transformation was typical of each cell line. Surprisingly, retransformation was not accompanied by the reappearance of detectable levels of E 1 a gene activity in the G2aAza and G5Aza cell lines. In search of a mechanistic explanation for the loss of gene activity in the revertants and its reappearance in the retransformants, we examined the state of methylation of the E I a gene region in these cells. Neither the Ela promoter nor its upstream region was methylated in the revertants or the 5-AzaC retransformants. These results suggest that E 1 a transcription was suppressed by mechanisms other than DNA methylation and that 5-AzaC could retransform these cells without lifting the Ela-suppressed state.

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Spontaneous and 5-azacytidine-induced reexpression of ornithine carbamoyl transferase in hepatoma cells.

Cited by 24 publications

References 29 publications

Expression of ornithine carbamoyltransferase gene in rat hepatoma-derived cell lines, H4-II-E and R-Y121B

Expression of ornithine carbamoyltransferase gene in rat hepatoma-derived cell lines, H4-II-E and R-Y121B

Arginine enzymatic deprivation and diet restriction for cancer treatment

Drug-induced revertants of adenovirus-transformed cells: retransformation by 5-azacytidine without reactivation of E1a

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