Effect of Microsomally Activated AFB1 on GGT Activity in 3 Rat Liver Cell Lines

Overview

Journal Br J Cancer

Specialty Oncology

Date 1982 Jun 1

PMID 6124269

Citations 1

Authors

M M Manson

J A Green

Affiliations

Soon will be listed here.

Abstract

Three cell lines derived from adult rat liver have been used to study changes in levels of gamma-glutamyl transferase (GGT), a possible marker for premalignant transformation in liver in vivo. None of the cell lines was able to metabolize aflatoxin B1 (AFB1) and treatment with AFB1 alone did not influence GGT activity. However, treatment with microsomally activated AFB1 increased the level of activity in a cell line (BL8L) derived from normal liver with very low levels of GGT, by as much as 10-fold, and 5-fold in a cell line (ARL) also isolated from normal rat liver, but which had subsequently undergone spontaneous transformation. Microsomes from rats pretreated with phenobarbitone were compared with those from 3-methylcholanthrene-treated animals. AFB1 activated by the former produced larger increases in GGT activity, but in no case did the enzyme levels approach that in a cell line (JBI) derived from a hepatoma in the liver of an AFB1-fed rat. Treatment of JBI cells with microsomally activated AFB1 produced no further increase in activity. Histochemical staining indicated an uneven distribution of enzyme in all cell populations, both before and after treatment. This cell-culture system is useful for further studies on the role of GGT in carcinogenesis.

Citing Articles

Some mass-spectral and n.m.r. analytical studies of a glutathione conjugate of aflatoxin B1.

Moss E, Judah D, Przybylski M, Neal G Biochem J. 1983; 210(1):227-33.

PMID: 6133517 PMC: 1154209. DOI: 10.1042/bj2100227.

References

Williams G, Ohmori T, Katayama S, Rice J . Alteration by phenobarbital of membrane-associated enzymes including gamma glutamyl transpeptidase in mouse liver neoplasms. Carcinogenesis. 1980; 1(10):813-8. DOI: 10.1093/carcin/1.10.813. View

Toyoshima K, Hiasa Y, Ito N, TSUBURA Y . In vitro malignant transformation of cells derived from rat liver by means of aflatoxin B1. Gan. 1970; 61(6):557-61. View

DIPAOLO J, Nelson R, Donovan P . In vitro transformation of Syrian hamster embryo cells by diverse chemical carcinogens. Nature. 1972; 235(5336):278-80. DOI: 10.1038/235278a0. View

Williams G, Elliott J, WEISBURGER J . Carcinoma after malignant conversion in vitro of epithelial-like cells from rat liver following exposure to chemical carcinogens. Cancer Res. 1973; 33(3):606-12. View

Kalengayi M, Ronchi G, Desmet V . Histochemistry of gamma-glutamyl transpeptidase in rat liver during aflatoxin B1-induced carcinogenesis. J Natl Cancer Inst. 1975; 55(3):579-88. DOI: 10.1093/jnci/55.3.579. View

Judah D, Legg R, Neal G . Development of resistance to cytotoxicity during aflatoxin carcinogenesis. Nature. 1977; 265(5592):343-5. DOI: 10.1038/265343b0. View

Solt D, Medline A, Farber E . Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Am J Pathol. 1977; 88(3):595-618. PMC: 2032374. View

Cheng S, Nassar K, Levy D . gamma-Glutamyltranspeptidase activity in normal, regenerating and malignant hepatocytes. FEBS Lett. 1978; 85(2):310-2. DOI: 10.1016/0014-5793(78)80480-3. View

Laishes B, Ogawa K, Roberts E, Farber E . Gamma-glutamyl transpeptidase: a positive marker for cultured rat liver cells derived from putative premalignant and malignant lesions. J Natl Cancer Inst. 1978; 60(5):1009-16. DOI: 10.1093/jnci/60.5.1009. View

10.

Schaeffer W, Heintz N . A diploid rat liver cell culture. IV. Malignant transformation by aflatoxin B1. In Vitro. 1978; 14(5):418-27. DOI: 10.1007/BF02616103. View

11.

Neal G, Colley P . Some high-performance liquid-chromatographic studies of the metabolism of aflatoxins by rat liver microsomal preparations. Biochem J. 1978; 174(3):839-51. PMC: 1185989. DOI: 10.1042/bj1740839. View

12.

Tate S, Meister A . Serine-borate complex as a transition-state inhibitor of gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1978; 75(10):4806-9. PMC: 336209. DOI: 10.1073/pnas.75.10.4806. View

13.

Sirica A, Richards W, Tsukada Y, Sattler C, Pitot H . Fetal phenotypic expression by adult rat hepatocytes on collagen gel/nylon meshes. Proc Natl Acad Sci U S A. 1979; 76(1):283-7. PMC: 382923. DOI: 10.1073/pnas.76.1.283. View

14.

Lowing R, Fry J, Jones C, Wiebkin P, King L, Bridges J . The early effects of chemical carcinogens on adult rat hepatocytes in primary culture: I. Quantitative changes in intracellular enzyme activities following a single dose of carcinogen. Chem Biol Interact. 1979; 24(2):121-31. DOI: 10.1016/0009-2797(79)90001-2. View

15.

Neal G, Colley P . The formation of 2,3-dihydro-2,3-dihydroxy aflatoxin B1 by the metabolism of aflatoxin B1 in vitro by rat liver microsomes. FEBS Lett. 1979; 101(2):382-6. DOI: 10.1016/0014-5793(79)81049-2. View

16.

Tsuchida S, Hoshino K, Sato T, Ito N, Sato K . Purification of gamma-glutamyltransferases from rat hepatomas and hyperplastic hepatic nodules, and comparison with the enzyme from rat kidney. Cancer Res. 1979; 39(10):4200-5. View

17.

FIALA S, Trout E, Ostrander H, FIALA A . gamma-Glutamyltransferase and the inhibition of azo dye-produced neoplasia by concomitant administration of disulfiram. J Natl Cancer Inst. 1980; 64(2):267-71. DOI: 10.1093/jnci/64.2.267. View

18.

Tsuda H, Lee G, Farber E . Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens. Cancer Res. 1980; 40(4):1157-64. View

19.

Smith G, Ding J, Peters T . A sensitive fluorimetric assay for gamma-glutamyl transferase. Anal Biochem. 1979; 100(1):136-9. DOI: 10.1016/0003-2697(79)90122-2. View

20.

Shinozuka H, Lombardi B . Synergistic effect of a choline-devoid diet and phenobarbital in promoting the emergence of foci of gamma-glutamyltranspeptidase-positive hepatocytes in the liver of carcinogen-treated rats. Cancer Res. 1980; 40(10):3846-9. View