Shifts in the extent and patterns of DNA methylation upon explantation and subcultivation of adenovirus type 12-induced hamster tumor cells

Kuhlmann, Ingrid; Doerfler, Walter

doi:10.1016/0042-6822(82)90330-0

Cited by 59 publications

(26 citation statements)

References 19 publications

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“…This finding is in good agreement with that made in Ad 12-induced hamster tumours (Kuhlmann & Doerfler, 1981).…”

Section: (B) Non-virus Eukaryotic Systemssupporting

confidence: 82%

“…Conversely, both Ad2 and Adl2 DNA can be extensively methylated when they are integrated into the host genome Sutter & Doerfler, 1979Vardimon et al, 1980;Eick et al, 1980;Kuhlmann & Doerfler, 1981). These findings strongly suggest that virus DNA can be de novo methylated, apparently during or after the incorporation into host chromatin.…”

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 54%

“…The integrated Adl2 DNA sequences in cell DNA extracted from tumours directly are poorly methylated at the 5'-CCGG-3' (HpaII/MspI) sites and at the 5'-GCGC-Y (HhaI) sites, Surprisingly, the extent and the patterns of methylation of the integrated Adl2 DNA sequences shift to higher levels when tumour cells are explanted and subcultivated repeatedly at passage levels 4 to 20. No further striking changes in methylation patterns are observed when the tumour cells are re-implanted into newborn hamsters nor when cells from these tumours are re-explanted and carried up to third passage or when several subclones of the tumour cells are examined (Kuhlmann & Doerfler, 1981).…”

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 99%

“…The presence of de novo methylases in mammalian cells has not yet been rigorously demonstrated. On the other hand, it is necessary to postulate the presence of such enzyme activities on the basis of the finding that adenovirus DNA integrated in the DNA of transformed and tumour cells is extensively methylated Sutter & Doerfler, 1979Vardimon et al, 1980;Kuhlmann & Doerfler, 1981). Perhaps, de novo methylases are only active in chromatin.…”

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 99%

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DNA Methylation--A Regulatory Signal in Eukaryotic Gene Expression

Doerfler

1981

Journal of General Virology

182

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“…This finding is in good agreement with that made in Ad 12-induced hamster tumours (Kuhlmann & Doerfler, 1981).…”

Section: (B) Non-virus Eukaryotic Systemssupporting

confidence: 82%

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 54%

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 99%

Section: On the Biological Function Of Dna Methylation A Signal Recogmentioning

confidence: 99%

See 2 more Smart Citations

DNA Methylation--A Regulatory Signal in Eukaryotic Gene Expression

Doerfler

1981

Journal of General Virology

182

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“…Long-term stability is a definitive characteristic of somatic cell mutants (53). In contrast, 5-azacytidine-induced phenotypes and methylation patterns are often unstable, particularly in culture (18,19,32,47,60,62; Kerbel et al, in press). The same seems to be true of some azacytidine-induced BHK transformants.…”

mentioning

confidence: 99%

Induction of a step in carcinogenesis that is normally associated with mutagenesis by nonmutagenic concentrations of 5-azacytidine.

Bouck¹,

Kokkinakis²,

Ostrowsky³

1984

Mol. Cell. Biol.

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The permanent cell line BHK-21/cl 13 can be transformed by mutagenic carcinogens as the result of the induction of a recessive somatic mutation. Yet when these cells were treated with 5-azacytidine under conditions in which no mutants resistant to either ouabain or 6-thioguanine could be detected, they were transformed efficiently. These transformants were induced, not selected. 6-Azacytidine was ineffective at transforming BHK cells; 2'-deoxy-5-azacytidine was exceptionally effective. When tested by cell fusion, transformants induced by 5-azacytidine fell into the same complementation group as those induced by highly mutagenic carcinogens, but they were phenotypically distinct in that they were unstable during prolonged passage and rarely displayed the temperature-limited phenotypes so common among BHK transformants induced by strongly mutagenic carcinogens. These results raise the possibility that a cell can be induced by either genetic or epigenetic means to traverse the same single step in carcinogenesis.It is generally accepted that mammalian cells can progress toward tumorigenicity as the result of mutagenic changes in base sequences in genomic DNA. Diverse observations suggesting that this is the case (5,30,39,49) have been confirmed by recent demonstrations that oncogenes can be activated effectively by a wide range of structural changes in DNA, including amplification and translocation of genes, insertion of promoters and enhancers, and base substitutions (reviewed in references 3, 34, and 36

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DNA-Methylierung: Geninaktivierung durch sequenzspezifische DNA-Methylierungen

Doerfler¹

1984

Angew. Chem.

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Bei molekularbiologischen Untersuchungen eukaryotischer Organismen spielt die Aufklarung der an der Regulation der Genexpression beteiligten Mechanismen eine wichtige Rolle. Alle Zellen eines Organismus enthalten die gleichen Gene, unterscheiden sich aber im Muster der Genexpression. Es gibt viele Hinweise darauf, daB das Expressionsmuster von Tumorzellen und normalen Zellen villlig verschieden ist. Ein eingehend untersuchtes molekulares Signal zur Regulation der Genexpression in Eukaryonten ist ein modifiziertes Nucleotid mit der Base 5-Methylcytosin (5-mC). An gut charakterisierten eukaryotischen Systemen konnte gezeigt werden, daR das Einfugen von 5-mC in spezifische Sequenzen, insbesondere in die Promotor-Regionen, eine Geninaktivierung bewirken kann. Studien an viralen und anderen eukaryotischen Systemen halfen, die Beziehung zwischen Ursache und Wirkung zu erkennen. Inaktive Gene sind haufig in der Promotor-Region hypermethyliert, aktive Gene sind hypomethyliert. Der biochemische Mechanismus, der einer Geninaktivierung durch Methylierungen spezifischer DNA-Sequenzen zugrunde liegt, konnte noch nicht aufgeklart werden. Es ist vorstellbar, daB Promotor-Methylierungen die Bindung zellularer F'roteine beeinflussen, die am Erkennen des Promotors eines Gens beteiligt sind. Strukturveranderungen durch Methylierung der DNA in Promotor-Regionen kijnnten ebenfalls eine wichtige Rolle spielen. Wahrscheinlich ist die DNA-Methylierung ein Signal, das zur Langzeitinaktivierung von Genen fiihrt, da man annehmen mul3, daR DNA-Methylierungsmuster nur durch DNA-Replikation und gleichzeitige spezifische Inhibierung postreplikativer Methylierungen verlndert werden k6nnen.

show abstract

Shifts in the extent and patterns of DNA methylation upon explantation and subcultivation of adenovirus type 12-induced hamster tumor cells

Cited by 59 publications

References 19 publications

DNA Methylation--A Regulatory Signal in Eukaryotic Gene Expression

DNA Methylation--A Regulatory Signal in Eukaryotic Gene Expression

Induction of a step in carcinogenesis that is normally associated with mutagenesis by nonmutagenic concentrations of 5-azacytidine.

DNA-Methylierung: Geninaktivierung durch sequenzspezifische DNA-Methylierungen

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