Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1975 Oct;32(4):440–450. doi: 10.1038/bjc.1975.245

The persistence of unmetabolized 3H-7,12-dimethylbenz(a)anthracene in regenerating rat liver.

R L Tomsak, R T Cook
PMCID: PMC2024757  PMID: 813754

Abstract

The hepatic subcellular distribution, binding and persistence of 3H-7,12-dimethylbenz(a)anthracene were compared in partially hepatectomized rats and in intact controls. By 2 weeks after injection, intact liver homogenates contained only 9% of the total radioactivity present 4 h after injection; regenerated liver contained 60% in spite of a tripling in liver mass during this time. Cell fractions isolated from regenerated liver had 9-59 fold greater hexane extractable specific activities than those from intact liver. The radioactivity present in hexane extracts co-chromatographed with a 3H-7,12-dimethylbenz(a)anthracene standard. Preliminary experiments demonstrated that liver microsomes isolated from DMBA treated partially hepatectomized animals metabolized less DMBA in vitro than did microsomes isolated from DMBA treated intact animals. The greater persistence of unmetabolized DMBA may be related to the greater carcinogenicity of this compound for regenerating, as compared with intact, rat liver.

Full text

PDF
440

Selected References

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

  1. ALLISON A. C., MALLUCCI L. UPTAKE OF HYDROCARBON CARCINOGENS BY LYSOSOMES. Nature. 1964 Sep 5;203:1024–1027. doi: 10.1038/2031024b0. [DOI] [PubMed] [Google Scholar]
  2. BOYLAND E., SIMS P. METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 7,12-DIMETHYLBENZ(ALPHA)ANTHRACENE BY RAT-LIVER HOMOGENATES. Biochem J. 1965 Jun;95:780–787. doi: 10.1042/bj0950780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BROOKES P., LAWLEY P. D. EVIDENCE FOR THE BINDING OF POLYNUCLEAR AROMATIC HYDROCARBONS TO THE NUCLEIC ACIDS OF MOUSE SKIN: RELATION BETWEEN CARCINOGENIC POWER OF HYDROCARBONS AND THEIR BINDING TO DEOXYRIBONUCLEIC ACID. Nature. 1964 May 23;202:781–784. doi: 10.1038/202781a0. [DOI] [PubMed] [Google Scholar]
  4. Blobel G., Potter V. R. Nuclei from rat liver: isolation method that combines purity with high yield. Science. 1966 Dec 30;154(3757):1662–1665. doi: 10.1126/science.154.3757.1662. [DOI] [PubMed] [Google Scholar]
  5. Booth J., Keysell G. R., Sims P. Formation of glutathione conjugates as metabolites of 7,12-dimethylbenz-(a)anthracene by rat-liver homogenates. Biochem Pharmacol. 1973 Jul 15;22(14):1781–1791. doi: 10.1016/0006-2952(73)90392-4. [DOI] [PubMed] [Google Scholar]
  6. Bresnick E., Liebelt R. A., Stevenson J. G., Madix J. C. The distribution of radioactivity within the hepatic cell after administration of labeled 3-methylcholanthrene. Cancer Res. 1967 Mar;27(3):462–468. [PubMed] [Google Scholar]
  7. Bürki K., Stoming T. A., Bresnick E. Effects of an epoxide hydrase inhibitor on in vivo binding of polycyclic hydrocarbons to DNA and on skin carcinogenesis. J Natl Cancer Inst. 1974 Mar;52(3):785–788. doi: 10.1093/jnci/52.3.785. [DOI] [PubMed] [Google Scholar]
  8. CALCUTT G., PAYNE S. The intracellular metabolism of 3:4 benzpyrene: further examination of the supernatant fraction from mouse liver. Br J Cancer. 1954 Sep;8(3):561–565. doi: 10.1038/bjc.1954.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CALCUTT G., PAYNE S. The intracellular metabolism of 3:4 benzpyrene: sites of oxidation in mouse liver. Br J Cancer. 1954 Sep;8(3):554–560. doi: 10.1038/bjc.1954.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CALCUTT G., PAYNE S. The intracellular metabolism of 3:4 benzpyrene; benzpyrene metabolites from rats and their sites of formation in rat liver. Br J Cancer. 1954 Dec;8(4):710–713. doi: 10.1038/bjc.1954.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. CALCUTT G. The distribution of polycyclic hydrocarbons within the cells of some mouse and rat tissues. Br J Cancer. 1958 Mar;12(1):149–160. doi: 10.1038/bjc.1958.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. CERIOTTI G. A microchemical determination of desoxyribonucleic acid. J Biol Chem. 1952 Sep;198(1):297–303. [PubMed] [Google Scholar]
  13. Chiesara E., Conti F., Meldolesi J. Influence of partial hepatectomy on the induction of liver microsomal drug-metabolizing enzymes produced by phenobarbital. A biochemical and ultrastructural study. Lab Invest. 1970 Apr;22(4):329–338. [PubMed] [Google Scholar]
  14. DOMSKY I. I., LIJINSKY W., SPENCER K., SHUBIK P. Rate of metabolism of 9,10-dimethyl-1,2-benzanthracene in newborn and adult mice. Proc Soc Exp Biol Med. 1963 May;113:110–112. doi: 10.3181/00379727-113-28292. [DOI] [PubMed] [Google Scholar]
  15. DePierre J. W., Moron M. S., Johannesen K. A., Ernster L. A reliable, sensitive, and convenient radioactive assay for benzpyrene monooxygenase. Anal Biochem. 1975 Feb;63(2):470–484. doi: 10.1016/0003-2697(75)90371-1. [DOI] [PubMed] [Google Scholar]
  16. Diamond L., Defendi V., Brookes P. The interaction of 7,12-dimethylbenz(a)anthracene with cells sensitive and resistant to toxicity induced by this carcinogen. Cancer Res. 1967 May;27(5):890–897. [PubMed] [Google Scholar]
  17. FOUTS J. R., DIXON R. L., SHULTICE R. W. The metabolism of drugs by regenerating liver. Biochem Pharmacol. 1961 Aug;7:265–270. doi: 10.1016/0006-2952(61)90093-4. [DOI] [PubMed] [Google Scholar]
  18. Flesher J. W., Sydnor K. L. Carcinogenicity of derivatives of 7,12-dimethylbenz(a)anthracene. Cancer Res. 1971 Dec;31(12):1951–1954. [PubMed] [Google Scholar]
  19. Goshman L. M., Heidelberger C. Binding of tritium-labeled polycyclic hydrocarbons to DNA of mouse skin. Cancer Res. 1967 Sep;27(9):1678–1688. [PubMed] [Google Scholar]
  20. Henderson P. T., Kersten K. J. Metabolism of drugs during rat liver regeneration. Biochem Pharmacol. 1970 Jul;19(7):2343–2351. doi: 10.1016/0006-2952(70)90133-4. [DOI] [PubMed] [Google Scholar]
  21. Janss D. H., Moon R. C., Irving C. C. The binding of 7,12-dimethylbenz(a)anthracene to mammary parenchyma DNA and protein in vivo. Cancer Res. 1972 Feb;32(2):254–258. [PubMed] [Google Scholar]
  22. Jellinck P. H., Smith G., Fletcher R. Nature of the water-soluble metabolites of 7,12-dimethylbenza(a)-anthracene formed by liver microsomes of normal and 3-methylcholanthrene-treated rats. Cancer Res. 1970 Jun;30(6):1715–1721. [PubMed] [Google Scholar]
  23. Jones P. A., Hawtrey A. O. Studies on the binding and distribution of radioactively labelled 3'-methylcholanthrene in subcellular fractions of rat liver. Br J Cancer. 1971 Dec;25(4):845–852. doi: 10.1038/bjc.1971.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Juhn S. K., Prodi G. The effect of 7,12-dimethylbenz(a)anthracene on the incorporation of thymidine-H3 into deoxyribonucleic acid in normal and regenerating liver. Experientia. 1965 Aug 15;21(8):473–474. doi: 10.1007/BF02150830. [DOI] [PubMed] [Google Scholar]
  25. Kuroki T., Heidelberger C. The binding of polycyclic aromatic hydrocarbons to the DNA, RNA, and proteins of transformable cells in culture. Cancer Res. 1971 Dec;31(12):2168–2176. [PubMed] [Google Scholar]
  26. 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]
  27. Lees M. B., Paxman S. Modification of the Lowry procedure for the analysis of proteolipid protein. Anal Biochem. 1972 May;47(1):184–192. doi: 10.1016/0003-2697(72)90291-6. [DOI] [PubMed] [Google Scholar]
  28. Levine W. G. Hepatic uptake, metabolism, and biliary excretion of 7,12-dimethylbenzanthracene in the rat. Drug Metab Dispos. 1974 Mar-Apr;2(2):169–177. [PubMed] [Google Scholar]
  29. Marquardt H., Bendich A., Philips F. S., Hoffmann D. Binding of (G- 3 H)-7,12-dimethylbenz(a)anthracene to DNA of normal and of rapidly dividing hepatic cells of rats. Chem Biol Interact. 1971 Feb;3(1):1–11. doi: 10.1016/0009-2797(71)90021-4. [DOI] [PubMed] [Google Scholar]
  30. Marquardt H., Heidelberger C. Influence of "feeder cells" and inducers and inhibition of microsomal mixed-function oxidases on hydrocarbon-induced malignant transformation of cells derived from C3H mouse prostate. Cancer Res. 1972 Apr;32(4):721–725. [PubMed] [Google Scholar]
  31. Marquardt H., Philips F. S., Bendich A. DNA binding and inhibition of DNA synthesis after 7,12-dimethylbenz(a)anthracene administered during the early prereplicative phase in regenerating rat liver. Cancer Res. 1972 Sep;32(9):1810–1813. [PubMed] [Google Scholar]
  32. Marquardt H., Philips F. S. The effects of 7,12-dimethylbenz(alpha)anthracene on the synthesis of nucleic acids in rapidly dividing hepatic cells in rats. Cancer Res. 1970 Jul;30(7):2000–2006. [PubMed] [Google Scholar]
  33. Marquardt H., Sapozink M. D., Zedeck M. S. Inhibition by cysteamine-HCl of oncogenesis induced by 7,12-dimethylbenz(alpha)anthracene without affecting toxicity. Cancer Res. 1974 Dec;34(12):3387–3390. [PubMed] [Google Scholar]
  34. Marquardt H., Sodergren J. E., Sims P., Grover P. L. Malignant transformation in vitro of mouse fibroblasts by 7,12-dimethylbenz(A)anthracene and 7-hydroxymethylbenz(A)anthracene and by their K-region derivatives. Int J Cancer. 1974 Mar 15;13(3):304–310. doi: 10.1002/ijc.2910130305. [DOI] [PubMed] [Google Scholar]
  35. Marquardt H., Sternberg S. S., Philips F. S. 7,12-dimethylbenz(a)anthracene and hepatic neoplasia in regenerating rat liver. Chem Biol Interact. 1970 Dec;2(4):401–403. doi: 10.1016/0009-2797(70)90060-8. [DOI] [PubMed] [Google Scholar]
  36. NAKAI T., SHUBIK P. AUTORADIOGRAPHIC LOCALIZATION OF TISSUE-BOUND TRITIATED 7,12-DIMETHYLBENZ(A)ANTHRACENE IN MOUSE SKIN 24 AND 48 HOURS AFTER SINGLE APPLICATION. J Natl Cancer Inst. 1964 Nov;33:887–891. doi: 10.1093/jnci/33.5.887. [DOI] [PubMed] [Google Scholar]
  37. Nebert D. W., Gielen J. E. Genetic regulation of aryl hydrocarbon hydroxylase induction in the mouse. Fed Proc. 1972 Jul-Aug;31(4):1315–1325. [PubMed] [Google Scholar]
  38. Pound A. W. Carcinogenesis and cell proliferation. N Z Med J. 1968 Jan;67(426 Suppl):88–99. [PubMed] [Google Scholar]
  39. Prodi G., Rocchi P., Grilli S. Binding of 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene to nucleic acids and proteins of organs in rats. Cancer Res. 1970 Apr;30(4):1020–1023. [PubMed] [Google Scholar]
  40. Rogan E. G., Cavalieri E. 3-Methylcholanthrene-inducible binding of aromatic hydrocarbons to DNA in purified rat liver nuclei. Biochem Biophys Res Commun. 1974 Jun 18;58(4):1119–1126. doi: 10.1016/s0006-291x(74)80259-7. [DOI] [PubMed] [Google Scholar]
  41. Schmutz J. A., Brownie A. C., Chaudhry A. P. 7, 12-Dimethylbenz(a)anthracene retention in the rat submandibular gland following intraglandular injection. Cancer Res. 1974 Mar;34(3):576–580. [PubMed] [Google Scholar]
  42. Schweppe J. S., Kot E., Jungmann R. A. Effects of gonadectomy on the uptake of polycyclic hydrocarbons by rat liver nuclei, DNA, and histones. Proc Soc Exp Biol Med. 1971 Oct;138(1):167–170. doi: 10.3181/00379727-138-35853. [DOI] [PubMed] [Google Scholar]
  43. Stoming T. A., Bresnick E. Hepatic epoxide hydrase in neonatal and partially hepatectomized rats. Cancer Res. 1974 Oct;34(10):2810–2813. [PubMed] [Google Scholar]
  44. TSO P. O., LU P. INTERACTION OF NUCLEIC ACIDS, II. CHEMICAL LINKAGE OF THE CARCINOGEN 3,4-BENZPYRENE TO DNA INDUCED BY PHOTORADIATION. Proc Natl Acad Sci U S A. 1964 Feb;51:272–280. doi: 10.1073/pnas.51.2.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wheatley D. N., Kernohan I. R., Currie A. R. Liver injury and the prevention of massive adrenal necrosis from 9, 10-dimethyl-1,2-benzanthracene in rats. Nature. 1966 Jul 23;211(5047):387–389. doi: 10.1038/211387a0. [DOI] [PubMed] [Google Scholar]
  46. von der DECKEN, HULTIN T. The enzymatic composition of rat liver microsomes during liver regeneration. Exp Cell Res. 1960 Apr;19:591–604. doi: 10.1016/0014-4827(60)90066-5. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES