Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1967 Oct;94(4):1025–1033. doi: 10.1128/jb.94.4.1025-1033.1967

Studies with Hydroxyurea VII. Hydroxyurea and the Synthesis of Functional Proteins

Herbert S Rosenkranz 1, Elaine B Winshell 1, Aiga Mednis 1, Howard S Carr 1, Cornelia J Ellner 1
PMCID: PMC276771  PMID: 4963772

Abstract

Hydroxyurea affected neither the synthesis nor the degradation of bacterial messenger-ribonucleic acid. The proteins made by hydroxyurea-treated cells were structurally intact and fully functional. Since the expression of the lethal action of hydroxyurea requires active protein production, the data indicate that treated cells do not die as the result of the synthesis of abnormal proteins.

Full text

PDF
1025

Images in this article

1030Image
on p.1030

Selected References

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

  1. ADAMSON R. H. ACTIVITY OF CONGENERS OF HYDROXYUREA AGAINST ADVANCED LEUKEMIA L1210. Proc Soc Exp Biol Med. 1965 Jun;119:456–458. doi: 10.3181/00379727-119-30209. [DOI] [PubMed] [Google Scholar]
  2. ALLEN D. W., ZAMECNIK P. C. The effect of puromycin on rabbit reticulocyte ribosomes. Biochim Biophys Acta. 1962 Jun 11;55:865–874. doi: 10.1016/0006-3002(62)90899-5. [DOI] [PubMed] [Google Scholar]
  3. BADER J. P. THE REQUIREMENT FOR DNA SYNTHESIS IN THE GROWTH OF ROUS SARCOMA AND ROUS-ASSOCIATED VIRUSES. Virology. 1965 Jun;26:253–261. doi: 10.1016/0042-6822(65)90272-2. [DOI] [PubMed] [Google Scholar]
  4. Bader J. P. Metabolic requirements for infection by Rous sarcoma virus. I. The transient requirement for DNA synthesis. Virology. 1966 Jul;29(3):444–451. doi: 10.1016/0042-6822(66)90220-0. [DOI] [PubMed] [Google Scholar]
  5. Brenner S., Stretton A. O., Kaplan S. Genetic code: the 'nonsense' triplets for chain termination and their suppression. Nature. 1965 Jun 5;206(988):994–998. doi: 10.1038/206994a0. [DOI] [PubMed] [Google Scholar]
  6. Brock T. D. CHLORAMPHENICOL. Bacteriol Rev. 1961 Mar;25(1):32–48. doi: 10.1128/br.25.1.32-48.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CHAMPE S. P., BENZER S. Reversal of mutant phenotypes by 5-fluorouracil: an approach to nucleotide sequences in messenger-RNA. Proc Natl Acad Sci U S A. 1962 Apr 15;48:532–546. doi: 10.1073/pnas.48.4.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. COHEN S. S. A hypothesis on a possible competitive relation between DNA synthesis and protein synthesis. Cancer Res. 1960 Jun;20:698–699. [PubMed] [Google Scholar]
  9. Carr H. S., Rosenkranz H. S. H3-thymidine and the conservation of deoxyribonucleic acid. J Bacteriol. 1966 Dec;92(6):1840–1841. doi: 10.1128/jb.92.6.1840-1841.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chaube S., Murphy M. L. The effects of hydroxyurea and related compounds on the rat fetus. Cancer Res. 1966 Jul;26(7):1448–1457. [PubMed] [Google Scholar]
  11. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DRAKULIC M., ERRERA M. Chloramphenicol-sensitive DNA synthesis in normal and irradiated bacteria. Biochim Biophys Acta. 1959 Feb;31(2):459–463. doi: 10.1016/0006-3002(59)90021-6. [DOI] [PubMed] [Google Scholar]
  13. ECHOLS H., GAREN A., GAREN S., TORRIANI A. Genetic control of repression of alkaline phosphatase in E. coli. J Mol Biol. 1961 Aug;3:425–438. doi: 10.1016/s0022-2836(61)80055-7. [DOI] [PubMed] [Google Scholar]
  14. Ellner P. D., Stoessel C. J., Drakeford E., Vasi F. A new culture medium for medical bacteriology. Am J Clin Pathol. 1966 Apr;45(4):502–504. doi: 10.1093/ajcp/45.4_ts.502. [DOI] [PubMed] [Google Scholar]
  15. FISHBEIN W. N., CARBONE P. P., FREIREICH E. J., MISRA D., FREI E., 3rd CLINICAL TRIALS OF HYDROXYUREA IN PATIENTS WITH CANCER AND LEUKEMIA. Clin Pharmacol Ther. 1964 Sep-Oct;5:574–580. doi: 10.1002/cpt196455574. [DOI] [PubMed] [Google Scholar]
  16. GALE G. R. EFFECT OF HYDROXYUREA ON THE INCORPORATION OF THYMIDINE INTO EHRLICH ASCITES TUMOR CELLS. Biochem Pharmacol. 1964 Oct;13:1377–1382. doi: 10.1016/0006-2952(64)90186-8. [DOI] [PubMed] [Google Scholar]
  17. GAREN A., SIDDIQI O. Suppression of mutations in the alkaline phosphatase structural cistron of E. coli. Proc Natl Acad Sci U S A. 1962 Jul 15;48:1121–1127. doi: 10.1073/pnas.48.7.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HAMERS R., HAMERS-CASTERMAN C. Synthesis by Escherichia coli of an abnormal beta-galactosidase in the presence of thiouracil. J Mol Biol. 1961 Apr;3:166–174. doi: 10.1016/s0022-2836(61)80043-0. [DOI] [PubMed] [Google Scholar]
  19. Kennedy B. J., Yarbro J. W. Metabolic and therapeutic effects of hydroxyurea in chronic myeloid leukemia. JAMA. 1966 Mar 21;195(12):1038–1043. [PubMed] [Google Scholar]
  20. LEVINTHAL C., KEYNAN A., HIGA A. Messenger RNA turnover and protein synthesis in B. subtilis inhibited by actinomycin D. Proc Natl Acad Sci U S A. 1962 Sep 15;48:1631–1638. doi: 10.1073/pnas.48.9.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. MORRIS A., ARLIGHAUS R., FAVELUKES S., SCHWEET R. INHIBITION OF HEMOGLOBIN SYNTHESIS BY PUROMYCIN. Biochemistry. 1963 Sep-Oct;2:1084–1090. doi: 10.1021/bi00905a030. [DOI] [PubMed] [Google Scholar]
  22. MURPHY M. L., CHAUBE S. PRELIMINARY SURVEY OF HYDROXYUREA (NSC-32065) AS A TERATOGEN. Cancer Chemother Rep. 1964 Aug;40:1–7. [PubMed] [Google Scholar]
  23. Margaretten W., Morgan C., Rosenkranz H. S., Rose H. M. Effect of hydroxyurea on virus development. I. Electron microscopic study of the effect on the development of bacteriophage T4. J Bacteriol. 1966 Feb;91(2):823–833. doi: 10.1128/jb.91.2.823-833.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. NATHANS D. INHIBITION OF PROTEIN SYNTHESIS BY PUROMYCIN. Fed Proc. 1964 Sep-Oct;23:984–989. [PubMed] [Google Scholar]
  25. Pollak R. D., Rosenkranz H. S. Metabolic effects of hydroxyurea on BHK-21 cells transformed with polyoma virus. Cancer Res. 1967 Jul;27(7):1214–1224. [PubMed] [Google Scholar]
  26. ROSENKRANZ H. S., BENDICH A. J., BEISER S. M. THE PROPERTIES OF THE ALKALINE PHOSPHATASE OF STREPTOMYCIN-DEPENDENT STRAINS OF ESCHERICHIA COLI. Biochim Biophys Acta. 1963 Nov 8;77:436–445. doi: 10.1016/0006-3002(63)90518-3. [DOI] [PubMed] [Google Scholar]
  27. ROSENKRANZ H. S., CARR H. S., ROSE H. M. PHENETHYL ALCOHOL. I. EFFECT ON MACROMOLECULAR SYNTHESIS OF ESCHERICHIA COLI. J Bacteriol. 1965 May;89:1354–1369. doi: 10.1128/jb.89.5.1354-1369.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. ROSENKRANZ H. S., LEVY J. A. HYDROXYUREA: A SPECIFIC INHIBITOR OF DEOXYRIBONUCLEIC ACID SYNTHESIS. Biochim Biophys Acta. 1965 Jan 11;95:181–183. doi: 10.1016/0005-2787(65)90225-x. [DOI] [PubMed] [Google Scholar]
  29. ROSENKRANZ H. S. Unusual alkaline phosphatase levels in streptomycin-dependent strains of E. coli. Biochemistry. 1963 Jan-Feb;2:122–125. doi: 10.1021/bi00901a021. [DOI] [PubMed] [Google Scholar]
  30. Rosenkranz H. S. An anomalous DNA component in hydroxyurea-treated Escherichia coli. Biochim Biophys Acta. 1966 Dec 21;129(3):618–621. doi: 10.1016/0005-2787(66)90077-3. [DOI] [PubMed] [Google Scholar]
  31. Rosenkranz H. S., Carr H. S. Studies with hydroxyurea. II. Prolonged exposure of Escherichia coli to hydroxyurea. J Bacteriol. 1966 Jul;92(1):178–185. doi: 10.1128/jb.92.1.178-185.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rosenkranz H. S., Garro A. J., Levy J. A., Carr H. S. Studies with hydroxyurea. I. The reversible inhibition of bacterial DNA synthesis and the effect of hydroxyurea on the bactericidal action of streptomycin. Biochim Biophys Acta. 1966 Mar 21;114(3):501–515. [PubMed] [Google Scholar]
  33. Rosenkranz H. S., Rose H. M., Morgan C., Hsu K. C. The effect of hydroxyurea on virus development. II. Vaccinia virus. Virology. 1966 Apr;28(4):510–519. doi: 10.1016/0042-6822(66)90235-2. [DOI] [PubMed] [Google Scholar]
  34. SEKIGUCHI M., COHEN S. S. The selective degradation of phage-induced ribonucleic acid by polynucleotide phosphorylase. J Biol Chem. 1963 Jan;238:349–356. [PubMed] [Google Scholar]
  35. STRETTON A. O., BRENNER S. MOLECULAR CONSEQUENCES OF THE AMBER MUTATION AND ITS SUPPRESSION. J Mol Biol. 1965 Jun;12:456–465. doi: 10.1016/s0022-2836(65)80268-6. [DOI] [PubMed] [Google Scholar]
  36. Schwartz H. S., Garofalo M., Sternberg S. S., Philips F. S. Hydroxyurea: inhibition of deoxyribonucleic acid synthesis in regenerating liver of rats. Cancer Res. 1965 Dec;25(11):1867–1870. [PubMed] [Google Scholar]
  37. TEMIN H. M. HOMOLOGY BETWEEN RNA FROM ROUS SARCOMA VIROUS AND DNA FROM ROUS SARCOMA VIRUS-INFECTED CELLS. Proc Natl Acad Sci U S A. 1964 Aug;52:323–329. doi: 10.1073/pnas.52.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. TEMIN H. M. MALIGNANT TRANSFORMATION IN CELL CULTURES. Health Lab Sci. 1964 Apr;1:79–83. [PubMed] [Google Scholar]
  39. TEMIN H. M. THE PARTICIPATION OF DNA IN ROUS SARCOMA VIRUS PRODUCTION. Virology. 1964 Aug;23:486–494. doi: 10.1016/0042-6822(64)90232-6. [DOI] [PubMed] [Google Scholar]
  40. TORRIANI A., ROTHMAN F. Mutants of Escherichia coli constitutive for alkaline phosphatase. J Bacteriol. 1961 May;81:835–836. doi: 10.1128/jb.81.5.835-836.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Temin H. M. Genetic and possible biochemical mechanisms in viral carcinogenesis. Cancer Res. 1966 Feb;26(2):212–216. [PubMed] [Google Scholar]
  42. YOUNG C. W., HODAS S. HYDROXYUREA: INHIBITORY EFFECT ON DNA METABOLISM. Science. 1964 Nov 27;146(3648):1172–1174. doi: 10.1126/science.146.3648.1172. [DOI] [PubMed] [Google Scholar]
  43. Yarbro J. W., Kennedy B. J., Barnum C. P. Hydroxyurea inhibition of DNA synthesis in ascites tumor. Proc Natl Acad Sci U S A. 1965 May;53(5):1033–1035. doi: 10.1073/pnas.53.5.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES