Skip to main content

Biological Markers Characterizing the Development of Preneoplastic and Neoplastic Lesions in Rodent Liver

  • Conference paper
Mouse Liver Tumors

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 10))

Abstract

The identification of biological “markers” indicating distinctively different functions between preneoplastic and neoplastic as compared with normal cells has been a subject of intensive investigation, especially as additional technology becomes available. Although no distinct single biochemical marker is ubiquitous to the process of neoplasia or even to a single histoge- netic type of neoplasm, a variety of histogenetic types of neoplasms in the human and experimental animals exhibit an extreme degree of marker or pheno- typic heterogeneity. Particularly well studied are markers which occurred during the process of hepatocarcinogenesis in the rodent as well as in its final product, the hepatoma. Although phenotypic heterogeneity is characteristic of hepatocellular carcinomas in both the rat and mouse, some degree of predominant marker pattern(s) has become apparent. In multistage hepatocarcinogenesis in the rat a frequent but not completely ubiquitous marker is the enzyme gamma-glutamyltranspeptidase. In the mouse, although such markers have not been as extensively studied as in the rat, glucose 6-phosphatase is a predominant but not exclusive histochemical marker. Many preneoplastic lesions occurring during the stage of promotion exhibit reduced levels of enzymes of oxidative xenobiotic metabolism, but this pattern is not ubiquitous. Studies on the transcription of specific genes in mouse liver as well as preneoplastic and neoplastic lesions in this tissue further demonstrate the phenotypic heterogeneity characteristic of differentiated hepatocellular carcinomas. In general, current evidence supports the two theses that 1) no single biologic marker or set of markers is uniquely characteristic of the preneoplas- tical and/or neoplastic phenotype and 2) marker or phenotypic heterogeneity is by far the rule rather than the exception in hepatocarcinogenesis in the rodent and quite possibly in all histogenetic types of neoplasms in mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Armuth V, Berenblum I (1977) Possible two-stage transplacental liver carcinogenesis in C57BL/6 mice. Int J Cancer 20: 292–295

    Article  PubMed  CAS  Google Scholar 

  • Boveri T (1914) Zur Frage der Entstehung maligner Tumoren. Gustav Fisher, Jena

    Google Scholar 

  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically-active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294–5299

    Article  PubMed  CAS  Google Scholar 

  • Coloma J, Pitot HC (1986) Characterization and sequence of a cDNA clone of gamma-glutamyltranspeptidase. Nuc Acids Res 14: 1393–1403

    Article  CAS  Google Scholar 

  • Custer RP, Sorof S (1984) Target polypeptide of a carcinogen is associated with normal mitosis and carcinogen-induced hyperplasias in adult hepatocytes. Proc Natl Acad Sci USA 81: 6738–6742

    Article  PubMed  CAS  Google Scholar 

  • Ellis RW, DeFeo D, Maryak JM, Young HA, Shih TY, Chang EH, Lowy DR, Scolnick EM (1980) Dual evolutionary origin for the rat genetic sequences of Harvey Murine Sarcoma Virus. J Virol 36: 408–420

    PubMed  CAS  Google Scholar 

  • Eriksson L, Ahluwalia M, Spiewak J, Lee G, Sarma DSR, Roomi MJ, Farber E (1983) Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis. Environ Health Persp 49: 171–174

    Article  CAS  Google Scholar 

  • Farber E (1973) Hyperplastic liver nodules. Methods Cancer Res 7: 345–375

    CAS  Google Scholar 

  • Fischer G, Ullrich D, Bock KW (1985) Effects of N-nitrosomorpholine and phenobarbital on UDP-glucuronyltransferase in putative preneoplastic foci of rat liver. Carcinogenesis 6: 605–609

    Article  PubMed  CAS  Google Scholar 

  • Forrester PI, Hancock RL (1978) Hepatocarcinogen-induced tRNA methylase activity in rat liver. Physiol Chem & Physics 10: 115–123

    CAS  Google Scholar 

  • Friedrich-Freksa H, Papadopulu G, Gössner W (1969) Histochemische Untersuchungen der Cancero- genese in der Rattenleber nach zeitlich begrenzter Verabfolgung von Diäthylnitrosamin. Z Krebsforsch 72: 240–253

    Article  PubMed  CAS  Google Scholar 

  • Glauert HP, Schwarz M, Pitot HC (1986) The phenotypic stability of altered hepatic foci: effect of the short-term withdrawal of phenobarbital and of the long-term feeding of purified diets after the withdrawal of phenobarbital. Carcinogenesis 7: 117–121

    Article  PubMed  CAS  Google Scholar 

  • Goldfarb S, Zak FG (1961) Role of injury and hyperplasia in the induction of hepatocellular carcinoma. J Am Med Assoc 178: 729–731

    CAS  Google Scholar 

  • Goldsworthy TL, Pitot HC (1985) The quantitative analysis and stability of histochemical markers of altered hepatic foci in rat liver following initiation by diethylnitrosamine administration and promotion with phenobarbital. Carcinogenesis 6: 1261–1269

    Article  PubMed  CAS  Google Scholar 

  • Greenstein JP (1954) Biochemistry of Cancer, 2nd ed. Academic Press, New York

    Google Scholar 

  • Greenstein JP (1956) Some biochemical characteristics of morphologically separable cancers. Cancer Res 16: 641–647

    PubMed  CAS  Google Scholar 

  • Hanigan MH, Pitot HC (1985) Gamma-glutamyltranspeptidase - its role in hepatocarcinogenesis. Carcinogenesis 6: 165–172

    Article  PubMed  CAS  Google Scholar 

  • Kitagawa T, Yokochi T, Sugano H (1972) a-Fetoprotein and hepatocarcinogenesis in rats fed 3-methyl-4-(dimethylamino)azobenzene or N-2-fluorenylacetamide. Int J Cancer 10: 368–381

    Google Scholar 

  • Kitagawa T, Watanabe R, Sugano H (1980) Induction of gamma-glutamyl transpeptidase activity by dietary phenobarbital in “spontaneous” hepatic tumors of C3H mice. Gann 71: 536–542

    PubMed  CAS  Google Scholar 

  • Kojima S, Hama Y, Kubodera A (1981) Glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase activities in the liver during chemically induced hepatocarcinogenesis in rats and mice. Toxicol Appl Pharmacol 60: 26–32

    Article  PubMed  CAS  Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1982) In: Molecular Cloning, A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory

    Google Scholar 

  • Mclntire KR (1984) Tumor markers: how useful are they? Hosp Pract 55–68

    Google Scholar 

  • Miller EC, Miller JA (1947) The presence and significance of bound aminoazo dyes in the livers of rats fed p-dimethylaminoazobenzene. Cancer Res 7: 468–475

    CAS  Google Scholar 

  • Moore MR, Pitot HC, Miller EC, Miller JA (1982) Induction of cholangiocellular carcinomas induced in Syrian golden hamsters administered aflatoxin B in large doses. J Natl Cancer Inst 68: 271–278

    PubMed  CAS  Google Scholar 

  • Naito M, Naito Y, Ito A (1982) Effect of phenobarbital on the development of tumors in mice treated neonatally with N-ethyl-N-nitrosourea. Gann 73: 111–114

    PubMed  CAS  Google Scholar 

  • Peraino C, Fry RJM, Staffeldt E, Kisieleski WE (1973) Effect of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res 33: 2701–2708

    PubMed  CAS  Google Scholar 

  • Peraino C, Richards WL, Stevens FJ (1983) Multistage hepatocarcinogenesis. In: Slaga TJ (ed) Mechanisms of Tumor Promoters. Volume 1 - Tumor Promotion in Internal Organs. CRC Press, Inc pp 1–53

    Google Scholar 

  • Peraino C, Staffeldt EF, Carnes BA, Ludeman VA, Blomquist JA, Vesselinovitch SD (1984) Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo(a)pyrene within one day after birth. Cancer Res 44: 3340–3347

    PubMed  CAS  Google Scholar 

  • Pereira MA, Knutsen GL, Herren-Freund SL (1985) Effect of subsequent treatment of chloroform or phenobarbital on the incidence of liver and lung tumors initiated by ethylnitrosourea in 15 day old mice. Carcinogenesis 6: 203–207

    Article  PubMed  CAS  Google Scholar 

  • Pitot HC (1963) Some biochemical essentials of malignancy. Cancer Res 23: 1474–1482

    PubMed  CAS  Google Scholar 

  • Pitot HC, Shires TK, Moyer G, Garrett CT (1974) Phenotypic variability as a manifestation of trans- lational control. In: Busch H (ed) The Molecular Biology of Cancer. Academic Press, New York, pp 523–534

    Google Scholar 

  • Pitot HC, Barsness L, Goldsworthy T, Kitagawa T (1978) Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271: 456–458

    Article  PubMed  CAS  Google Scholar 

  • Potter VR, Watanabe M, Pitot HC, Morris HP (1969) Systematic oscillations in metabolic activity in rat liver and hepatomas. Survey of normal diploid and other hepatoma lines. Cancer Res 29: 55–78

    PubMed  CAS  Google Scholar 

  • Pugh TD, Goldfarb S (1978) Quantitative histochemical and autoradiographic studies of hepatocarcinogenesis in rats fed 2-acetylaminofluorene followed by phenobarbital. Cancer Res 38: 4450–4457

    PubMed  CAS  Google Scholar 

  • Rao MS, Lalwani ND, Scarpelli DG, Reddy JK (1982) The absence of gamma-glutamyl transpeptidase activity in putative preneoplastic lesions and in hepatocellular carcinomas induced in rats by the hypolipidemic peroxisome proliferator Wy-14,643. Carcinogenesis 3: 1231–1233

    Article  PubMed  CAS  Google Scholar 

  • Reid E (1962) Significant biochemical effects of hepatocarcinogens in the rat: a review. Cancer Res 22: 398–399

    PubMed  CAS  Google Scholar 

  • Reynolds RD, Potter VR, Pitot HC, Reuber MD (1971) Survey of some enzyme patterns in transplantable Reuber mouse hepatomas. Cancer Res 31: 808–812

    PubMed  CAS  Google Scholar 

  • Satoh K, Kitahara A, Soma Y, Inaba Y, Hatayama I, Sato K (1985) Purification, induction, and distribution of placental glutathione transferase: A new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis. Proc Natl Acad Sci USA 82: 3964–3968

    Article  PubMed  CAS  Google Scholar 

  • Scherer E, Emmelot P (1976) Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. Cancer Res 36: 2544–2554

    PubMed  CAS  Google Scholar 

  • Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1982) Response of liver foci in rats to hepatic tumor promoters. Toxicol Pathol 10: 63–70

    Article  CAS  Google Scholar 

  • Schulte-Hermann R, Roome N, Timmermann-Trosiener I, Schuppler J (1984) Immunocytochemical demonstration of a phenobarbital-inducible cytochrome P450 in putative preneoplastic foci of rat liver. Carcinogenesis 5: 149–153

    Article  PubMed  CAS  Google Scholar 

  • Shen-Ong GLC, Keath EJ, Piccoli SP, Cole MD (1982) Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell 31: 443–452

    Article  PubMed  CAS  Google Scholar 

  • Simickova M, Dolezalova V, Nemecek R (1980) Correlation of deoxycytidylate deaminase activity with cell proliferation during hepatocarcinogenesis and tumour growth in transplantable rat hepatomas. Folia biologica 26: 194–203

    PubMed  CAS  Google Scholar 

  • Simmons DL, Lalley PA, Kasper CB (1985) Chromosomal assignments of genes coding for components of the mixed-function oxidase system in mice. J Biol Chem 260: 515–521

    PubMed  CAS  Google Scholar 

  • Sirica AE, Jicinsky JK, Heyer EK (1984) Effect of chronic phenobarbital administration on the gamma-glutamyl transpeptidase activity of hyperplastic liver lesions induced in rats by the Solt/Farber initiation: selection process of hepatocarcinogenesis. Carcinogenesis 5: 1737–1740

    Article  PubMed  CAS  Google Scholar 

  • Tazawa J, Irie T, French SW (1983) Mallory body formation runs parallel to gamma-glutamyl transferase induction in hepatocytes of griseofulvin-fed mice. Hepatology 6: 989–1001

    Google Scholar 

  • Warburg O (1930) Metabolism of tumors (translated by F. Dickens). Constable, London Ward JM, Rice JM, Creasia D, Lynch P, Riggs C (1983) Dissimilar patterns of promotion by di(2-eth- ylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice. Carcinogenesis 4: 1021–1029

    Article  Google Scholar 

  • Ward JM, Rice JM, Creasia D, Lynch P, Riggs C (1983) Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of heparocllular neoplasia initiated by diethylnitrosamine in B6C3F1 mice. Cacinogenesis 4:1021-1029

    Google Scholar 

  • Weber G (1982) Markers of malignancy in cancer cells. Proceedings of the Sixth Meeting of the European Association for Cancer Research, Budapest, 12–15 October 1981, pp 335–345

    Google Scholar 

  • Williams GM, Ohmori T, Katayama S, Rice JM (1980) Alteration by phenobarbital of membrane-associated enzymes including gamma glutamyl transpeptidase in mouse liver neoplasms. Carcinogenesis 1: 813–818

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer-Verlag

About this paper

Cite this paper

Beer, D.G., Pitot, H.C. (1987). Biological Markers Characterizing the Development of Preneoplastic and Neoplastic Lesions in Rodent Liver. In: Chambers, P.L., Henschler, D., Oesch, F. (eds) Mouse Liver Tumors. Archives of Toxicology, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71617-1_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71617-1_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-17124-9

  • Online ISBN: 978-3-642-71617-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics