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. 1977 Dec;89(3):671–684.

Reversible suppression of malignancy and differentiation of melanoma cells.

S Silagi
PMCID: PMC2032265  PMID: 596422

Abstract

Tumorigenicity is reversibly suppressed in mouse melanoma cells grown with 5-bromodeoxyuridine (BrdU). The nontumorigenic cells are immunogenic, and preinjection of these cells can protect mice against tumors inevitably formed when the parental, untreated melanoma cells are inoculated into inbred strain C57BL/6. A mixture of highly immunogenic clone, C(3)471, with malignant cells is also nontumorigenic. These effects are related to the host immune response since they occur only in immunocompetent mice. BrdU also reversibly suppresses functions related to pigment formation and plasminogen activation. These effects require incorporation of BrdU into DNA, emphasizing the value of the thymidine analog, BrdU as a tool to relate normal regulation of gene activity to perturbations of this regulation which produce malignant cells. This research can facilitate basic understanding of the malignant state and its relationship to host response as well as a method for immunizing melanoma patients after surgery to prevent tumor recurrence.

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Selected References

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

  1. Bischoff R., Holtzer H. Inhibition of myoblast fusion after one round of DNA synthesis in 5-bromodeoxyuridine. J Cell Biol. 1970 Jan;44(1):134–150. doi: 10.1083/jcb.44.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Christman J. K., Silagi S., Newcomb E. W., Silverstein S. C., Acs G. Correlated suppression by 5-bromodeoxyuridine of tumorigenicity and plasminogen activator in mouse melanoma cells. Proc Natl Acad Sci U S A. 1975 Jan;72(1):47–50. doi: 10.1073/pnas.72.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Rifkin D. B., Loeb J. N., Moore G., Reich E. Properties of plasminogen activators formed by neoplastic human cell cultures. J Exp Med. 1974 May 1;139(5):1317–1328. doi: 10.1084/jem.139.5.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Roblin R. O., Hammond M. E., Bensky N. D., Dvorak A. M., Dvorak H. F., Black P. H. Generation of macrophage migration inhibitory activity by plasminogen activators. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1570–1574. doi: 10.1073/pnas.74.4.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Rutter W. J., Pictet R. L., Morris P. W. Toward molecular mechanisms of developmental processes. Annu Rev Biochem. 1973;42:601–646. doi: 10.1146/annurev.bi.42.070173.003125. [DOI] [PubMed] [Google Scholar]
  6. Schulman J. D., Wrathall J. R., Silagi S., Doores L. Altered amino acid concentrations accompanying suppression of malignancy of mouse melanoma cells by 5-bromodeoxyuridine. J Natl Cancer Inst. 1974 Jan;52(1):275–277. doi: 10.1093/jnci/52.1.275. [DOI] [PubMed] [Google Scholar]
  7. Silagi S., Beju D., Wrathall J., Deharven E. Tumorigenicity, immunogenicity, and virus production in mouse melanoma cells treated with 5-bromodeoxyuridine. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3443–3447. doi: 10.1073/pnas.69.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Silagi S., Bruce S. A. Suppression of malignancy and differentiation in melanotic melanoma cells. Proc Natl Acad Sci U S A. 1970 May;66(1):72–78. doi: 10.1073/pnas.66.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Silagi S. Effects of 5-bromodeoxyuridine on tumorigenicity, immunogenicity, virus production, plasminogen activator, and melanogenesis of mouse melanoma cells. Int Rev Cytol. 1976;45:65–111. doi: 10.1016/s0074-7696(08)60078-9. [DOI] [PubMed] [Google Scholar]
  10. Silagi S. Modification of malignancy by 5-bromodeoxyuridine. Studies of reversibility and immunological effects. In Vitro. 1971 Sep-Oct;7(2):105–114. doi: 10.1007/BF02628269. [DOI] [PubMed] [Google Scholar]
  11. Silagi S., Newcomb E. W., Weksler M. E. Relationship of antigenicity of melanoma cells grown in 5-bromodeoxyuridine to reduced tumorigenicity. Cancer Res. 1974 Jan;34(1):100–104. [PubMed] [Google Scholar]
  12. Teich N., Lowy D. R., Hartley J. W., Rowe W. P. Studies of the mechanism of induction of infectious murine leukemia virus from AKR mouse embryo cell lines by 5-iododeoxyuridine and 5-bromodeoxyuridine. Virology. 1973 Jan;51(1):163–173. doi: 10.1016/0042-6822(73)90376-0. [DOI] [PubMed] [Google Scholar]
  13. Wrathall J. R., Newcomb E. W., Balint R., Zeitz L., Silagi S. Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions. J Cell Physiol. 1975 Dec;86 (Suppl 2)(3 Pt 2):581–592. doi: 10.1002/jcp.1040860503. [DOI] [PubMed] [Google Scholar]
  14. Wrathall J. R., Oliver C., Silagi S., Essner E. Suppression of pigmentation in mouse melanoma cells by 5-bromodeoxyuridine: effects on tyrosinase activity and melanosome formation. J Cell Biol. 1973 May;57(2):406–423. doi: 10.1083/jcb.57.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zeitz L., Lee R. Element analysis in labeled DNA by x-ray fluorescence. Anal Biochem. 1968 Jun;23(3):442–458. doi: 10.1016/0003-2697(68)90236-4. [DOI] [PubMed] [Google Scholar]

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