Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1967 Jun;103(3):692–698. doi: 10.1042/bj1030692

The effect of a single intraperitoneal dose of the hepatocarcinogen 4-dimethylaminoazobenzene on the rough-surfaced endoplasmic reticulum of the liver of the rat

B Ketterer 1, S J Holt 1, Patricia Ross-Mansell 1
PMCID: PMC1270469  PMID: 4963458

Abstract

1. Changes in the structure and function of the rough-surfaced endoplasmic reticulum of the rat liver as deduced by electron microscopy, polysome analysis and the amino acid-incorporating activity of microsome fractions have been followed at various time-intervals after a single intraperitoneal dose of the hepatocarcinogen 4-dimethylaminoazobenzene. 2. The earliest effect observed was detachment of polysomes and disorganization and vesiculation of the cisternae of the rough-surfaced endoplasmic reticulum. This occurred after 6hr. 3. Subsequent to this was a phase of polysome disaggregation accompanied by impaired amino acid-incorporating activity by microsomes together with a much enhanced stimulating effect of polyuridylic acid on amino acid uptake. This reached a maximum at 24hr. 4. By 40hr. polysomes had re-formed and the amino acid-incorporating activity, together with the polyuridylic acid effect, were similar to those in controls. 5. It was not until 112hr. that something like the normal structure of the rough-surfaced endoplasmic reticulum was re-established. 6. It is not yet possible to relate these changes specifically with the process of azo-dye carcinogenesis.

Full text

PDF
692

Images in this article

Selected References

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

  1. BAGLIO C. M., FARBER E. CORRESPONDENCE BETWEEN RIBOSOME AGGREGATION PATTERNS IN RAT LIVER HOMOGENATES AND IN ELECTRON MICROGRAPHS FOLLOWING ADMINISTRATION OF ETHIONINE. J Mol Biol. 1965 Jun;12:466–467. doi: 10.1016/s0022-2836(65)80269-8. [DOI] [PubMed] [Google Scholar]
  2. Clifford J. I., Rees K. R. Aflatoxin: a site of action in the rat liver cell. Nature. 1966 Jan 15;209(5020):312–313. doi: 10.1038/209312a0. [DOI] [PubMed] [Google Scholar]
  3. Daudel P., Jacquier A., Touplain A. Effet de quelques azoïques sur l'incorporation de l-leucine par un système microsomal de foie. C R Acad Sci Hebd Seances Acad Sci D. 1965 May 3;260(18):4871–4873. [PubMed] [Google Scholar]
  4. HENSHAW E. C., BOJARSKI T. B., HIATT H. H. PROTEIN SYNTHESIS BY FREE AND BOUND RAT LIVER RIBOSOMES IN VIVO AND IN VITRO. J Mol Biol. 1963 Aug;7:122–129. doi: 10.1016/s0022-2836(63)80041-8. [DOI] [PubMed] [Google Scholar]
  5. Hawtrey A. O., Nourse L. D. The effect of 4-dimethylamino-3'-methylazobenzene on 14-C-labelled amino acid incorporation by rat-liver polysome preparations. Biochem J. 1966 Mar;98(3):682–688. doi: 10.1042/bj0980682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hawtrey A. O., Schirren V., Dijkstra J. Studies on azo-dye carcinogenesis in rat liver. The effect of 4-dimethylamino-3'-methylazobenzene on the incorporation of [C]leucine into rat-liver microsomal protein. Biochem J. 1963 Jul;88(1):106–114. doi: 10.1042/bj0880106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LAFONTAINE J. G., ALLARD C. A LIGHT AND ELECTRON MICROSCOPE STUDY OF THE MORPHOLOGICAL CHANGES INDUCED IN RAT LIVER CELLS BY THE AZO DYE 2-ME-DAB. J Cell Biol. 1964 Jul;22:143–172. doi: 10.1083/jcb.22.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MAGEE P. N. Toxic liver injury; inhibition of protein synthesis in rat liver by dimethylnitrosamine in vivo. Biochem J. 1958 Dec;70(4):606–611. doi: 10.1042/bj0700606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MAGER J., BORNSTEIN S., HALBREICH A. ENHANCEMENT OF THE POLYURIDYLIC ACID-DIRECTED PHENYLALANINE POLYMERIZATION IN LIVER-MICROSOME PREPARATIONS FROM RATS TREATED WITH CARBON TETRACHLORIDE OR DIMETHYLNITROSAMINE. Biochim Biophys Acta. 1965 Apr 19;95:682–684. doi: 10.1016/0005-2787(65)90528-9. [DOI] [PubMed] [Google Scholar]
  12. MIZRAHI I. J., EMMELOT P. ON THE MODE OF ACTION BY WHICH THE CARCINOGEN DIMETHYLNITROSAMINE INHIBITS PROTEIN SYNTHESIS IN THE LIVER. Biochim Biophys Acta. 1964 Oct 16;91:362–364. doi: 10.1016/0926-6550(64)90271-3. [DOI] [PubMed] [Google Scholar]
  13. MUKHERJEE T., GUSTAFSSON R. G., AFZELIUS B. A., ARRHENIUS E. EFFECTS OF CARCINOGENIC AMINES ON AMINO ACID INCORPORATION BY LIVER SYSTEMS. II. A MORPHOLOGICAL AND BIOCHEMICAL STUDY ON THE EFFECT OF DIMETHYLNITROSAMINE. Cancer Res. 1963 Jul;23:944–953. [PubMed] [Google Scholar]
  14. Ma M. H., Webber A. J. Fine structure of liver tumors induced in the rat by 3'-methyl-4-dimethylaminoazobenzene. Cancer Res. 1966 May;26(5):935–946. [PubMed] [Google Scholar]
  15. PORTER K. R., BRUNI C. An electron microscope study of the early effects of 3'-Me-DAB on rat liver cells. Cancer Res. 1959 Nov;19:997–1009. [PubMed] [Google Scholar]
  16. PORTER K. R., BRUNI C. COMPARATIVE FINE STRUCTURE OF SLOW- AND FAST-GROWING HEPATOMAS. Acta Unio Int Contra Cancrum. 1964;20:1271–1274. [PubMed] [Google Scholar]
  17. REICH E., FRANKLIN R. M., SHATKIN A. J., TATUM E. L. Effect of actinomycin D on cellular nucleic acid synthesis and virus production. Science. 1961 Aug 25;134(3478):556–557. doi: 10.1126/science.134.3478.556. [DOI] [PubMed] [Google Scholar]
  18. REVEL M., HIATT H. H., REVEL J. P. ACTINOMYCIN D: AN EFFECT ON RAT LIVER HOMOGENATES UNRELATED TO ITS ACTION ON RNA SYNTHESIS. Science. 1964 Dec 4;146(3649):1311–1313. doi: 10.1126/science.146.3649.1311. [DOI] [PubMed] [Google Scholar]
  19. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SABATINI D. D., BENSCH K., BARRNETT R. J. Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation. J Cell Biol. 1963 Apr;17:19–58. doi: 10.1083/jcb.17.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SMUCKLER E. A., BENDITT E. P. STUDIES ON CARBON TETRACHLORIDE INTOXICATION. 3. A SUBCELLULAR DEFECT IN PROTEIN SYNTHESIS. Biochemistry. 1965 Apr;4:671–679. doi: 10.1021/bi00880a009. [DOI] [PubMed] [Google Scholar]
  22. WETTSTEIN F. O., STAEHELIN T., NOLL H. Ribosomal aggregate engaged in protein synthesis: characterization of the ergosome. Nature. 1963 Feb 2;197:430–435. doi: 10.1038/197430a0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES