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. 1988 Dec;85(23):9066–9070. doi: 10.1073/pnas.85.23.9066

Deletion of transfected oncogenes from NIH 3T3 transformants by inhibitors of poly(ADP-ribose) polymerase.

M Nakayasu 1, H Shima 1, S Aonuma 1, H Nakagama 1, M Nagao 1, T Sugimura 1
PMCID: PMC282664  PMID: 3143113

Abstract

a1-1 cells, a transformant line obtained by transfection of NIH 3T3 cells with human c-Ha-rasT24 (hc-Ha-rasT24), were converted to morphologically normal flat cells following a 2-week culture in the presence of benzamide (BA), an inhibitor of poly(ADP-ribose) polymerase [ADP-ribosyltransferase (polymerizing); EC 2.4.2.30]. Concomitant with these morphological changes was the loss of the exogenous hc-Ha-rasT24 sequence. When cells were cultured without transfer, multiple clusters of flat revertant cells surrounded by transformed cells within single colonies of a1-1 cells were observed. This, together with the slow growth rate of flat cells in the presence of BA, indicated that flat revertants were induced rather than selected by BA. Flat cells isolated from mixed colonies completely lost the exogenous and amplified hc-Ha-rasT24 gene. In contrast, the endogenous mouse c-Ha-ras in flat revertant cells was not lost during culture with BA. Similarly, the endogenous hc-Ha-rasT24 in human bladder carcinoma T24 cells was not affected by BA. By using various chemicals, it was suggested that inhibition of poly(ADP-ribose) polymerase induces an efficient and specific loss of the exogenous transforming genes including Ki-ras, N-ras, c-raf, and ret-II.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alkhatib H. M., Chen D. F., Cherney B., Bhatia K., Notario V., Giri C., Stein G., Slattery E., Roeder R. G., Smulson M. E. Cloning and expression of cDNA for human poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1224–1228. doi: 10.1073/pnas.84.5.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bürkle A., Meyer T., Hilz H., zur Hausen H. Enhancement of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA amplification in a Simian virus 40-transformed Chinese hamster cell line by 3-aminobenzamide. Cancer Res. 1987 Jul 15;47(14):3632–3636. [PubMed] [Google Scholar]
  3. Cherney B. W., McBride O. W., Chen D. F., Alkhatib H., Bhatia K., Hensley P., Smulson M. E. cDNA sequence, protein structure, and chromosomal location of the human gene for poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8370–8374. doi: 10.1073/pnas.84.23.8370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ellis R. W., DeFeo D., Maryak J. M., Young H. A., Shih T. Y., Chang E. H., Lowy D. R., Scolnick E. M. Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus. J Virol. 1980 Nov;36(2):408–420. doi: 10.1128/jvi.36.2.408-420.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Exley R., Gordon J., Clemens M. J. Induction of B-cell differentiation antigens in interferon- or phorbol ester-treated Daudi cells is impaired by inhibitors of ADP-ribosyltransferase. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6467–6470. doi: 10.1073/pnas.84.18.6467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Farzaneh F., Zalin R., Brill D., Shall S. DNA strand breaks and ADP-ribosyl transferase activation during cell differentiation. Nature. 1982 Nov 25;300(5890):362–366. doi: 10.1038/300362a0. [DOI] [PubMed] [Google Scholar]
  7. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B., Droller M. J., Baylin S. B., Nelkin B. D. Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer. Science. 1983 Jun 10;220(4602):1175–1177. doi: 10.1126/science.6304875. [DOI] [PubMed] [Google Scholar]
  9. Ishizaka Y., Tahira T., Ochiai M., Ikeda I., Sugimura T., Nagao M. Molecular cloning and characterization of human ret-II oncogene. Oncogene Res. 1988 Sep;3(2):193–197. [PubMed] [Google Scholar]
  10. Kurosaki T., Ushiro H., Mitsuuchi Y., Suzuki S., Matsuda M., Matsuda Y., Katunuma N., Kangawa K., Matsuo H., Hirose T. Primary structure of human poly(ADP-ribose) synthetase as deduced from cDNA sequence. J Biol Chem. 1987 Nov 25;262(33):15990–15997. [PubMed] [Google Scholar]
  11. Lönn U., Lönn S. Accumulation of 10-kilobase DNA replication intermediates in cells treated with 3-aminobenzamide. Proc Natl Acad Sci U S A. 1985 Jan;82(1):104–108. doi: 10.1073/pnas.82.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Milam K. M., Cleaver J. E. Inhibitors of poly(adenosine diphosphate-ribose) synthesis: effect on other metabolic processes. Science. 1984 Feb 10;223(4636):589–591. doi: 10.1126/science.6420886. [DOI] [PubMed] [Google Scholar]
  13. Nitta N., Ochiai M., Nagao M., Sugimura T. Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient. Jpn J Cancer Res. 1987 Jan;78(1):21–26. [PubMed] [Google Scholar]
  14. Oikawa A., Tohda H., Kanai M., Miwa M., Sugimura T. Inhibitors of poly(adenosine diphosphate ribose) polymerase induce sister chromatid exchanges. Biochem Biophys Res Commun. 1980 Dec 31;97(4):1311–1316. doi: 10.1016/s0006-291x(80)80009-x. [DOI] [PubMed] [Google Scholar]
  15. Oka J., Ueda K., Hayaishi O., Komura H., Nakanishi K. ADP-ribosyl protein lyase. Purification, properties, and identification of the product. J Biol Chem. 1984 Jan 25;259(2):986–995. [PubMed] [Google Scholar]
  16. Sugimura T. Poly(adenosine diphosphate ribose). Prog Nucleic Acid Res Mol Biol. 1973;13:127–151. doi: 10.1016/s0079-6603(08)60102-6. [DOI] [PubMed] [Google Scholar]
  17. Suzuki H., Uchida K., Shima H., Sato T., Okamoto T., Kimura T., Miwa M. Molecular cloning of cDNA for human poly(ADP-ribose) polymerase and expression of its gene during HL-60 cell differentiation. Biochem Biophys Res Commun. 1987 Jul 31;146(2):403–409. doi: 10.1016/0006-291x(87)90543-2. [DOI] [PubMed] [Google Scholar]
  18. Tahira T., Hayashi K., Ochiai M., Tsuchida N., Nagao M., Sugimura T. Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene. Mol Cell Biol. 1986 Apr;6(4):1349–1351. doi: 10.1128/mcb.6.4.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tahira T., Ochiai M., Hayashi K., Nagao M., Sugimura T. Activation of human c-raf-1 by replacing the N-terminal region with different sequences. Nucleic Acids Res. 1987 Jun 25;15(12):4809–4820. doi: 10.1093/nar/15.12.4809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Terada M., Fujiki H., Marks P. A., Sugimura T. Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6411–6414. doi: 10.1073/pnas.76.12.6411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tseng A., Jr, Lee W. M., Jakobovits E. B., Kirsten E., Hakam A., McLick J., Buki K., Kun E. Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1107–1111. doi: 10.1073/pnas.84.4.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Uchida K., Morita T., Sato T., Ogura T., Yamashita R., Noguchi S., Suzuki H., Nyunoya H., Miwa M., Sugimura T. Nucleotide sequence of a full-length cDNA for human fibroblast poly(ADP-ribose) polymerase. Biochem Biophys Res Commun. 1987 Oct 29;148(2):617–622. doi: 10.1016/0006-291x(87)90921-1. [DOI] [PubMed] [Google Scholar]

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