The possibility that the presence of malignant disease can influence the metabolic activation of two carcinogens, 2-acetylaminofluorene and aflatoxin B1, has been investigated in a group of patients with secondary carcinoma of the liver. Mutagenic activation by subcellular fractions from biopsy samples from the patients was determined in the Ames/Salmonella test and the results compared with those obtained from a group of control patients. No significant differences were observed between the groups of patients in their ability to activate the two compounds to mutagenic metabolites. A tenfold range in ability to activate aflatoxin B1 was observed whereas only a threefold range was obtained with 2-acetylaminofluorene. Human liver activates aflatoxin B1 approximately 100 times more efficiently than 2-acetylaminofluorene, a proven carcinogen in many species. This raises the question of the true risk to man from hepatocarcinogenicity from aflatoxin B1.
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References
1.
Ames, B.N., McCann, J. & Yamasaki, E. (1975). Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat. Res., 31, 347-364.
2.
Ames, B.N., Gurney, E.G., Miller, J.A. & Bartsch, H. (1972). Carcinogens as frameshift mutagens: metabolites and derivatives of 2-acetylaminofluorene and other aromatic amine carcinogens. Proc. NatlAcad. Sci. USA, 69, 3128-3132.
3.
Atlas, S.A., Vesell, E.S. & Nebert, D.W. (1976). Genetic control of inter-individual variations in the inducibility of aryl hydrocarbon hydroxylase in cultured human lymphocytes . Cancer Res., 36, 4619-4630.
4.
Boulos, B.M., Macdougall, M., Shoeman, D.W. & Azarnoff, D.L. (1972). Evidence that inhibition of hepatic drug oxidation by tumours is mediated by a circulating humor. Proc. Soc. Exp. Biol. Med., 139, 1353-1355.
5.
Bridges, J.W. (1980). The role of the drug-metabolizing enzymes. In Environmental Chemicals, Enzyme Function and Human Disease, Ciba Foundation Symposium 76 (new series), pp. 5-24. Amsterdam : Excerpta Medica.
6.
Conney, A.H., Pantuck, E.J., Pantuck, C.B., Fortner, J.G., Alvares, A.P., Anderson, K.E. & Kappas, A. (1980). Variability in human drug metabolism. In Clinical Pharmacology and Therapeutics. Proceedings of the First World Conference, ed. P. Turner, pp. 51-62. London: Macmillan .
7.
Croy, R.G. & Wogan, G.N. (1981). Quantitative comparison of covalent aflatoxin - DNA adducts formed in rat and mouse livers and kidneys. J. Natl Cancer Inst., 66, 761-768.
8.
Degen, G.H. & Neumann, H.G. (1981). Differences in aflatoxin B1-susceptibility of rat and mouse are correlated with the capability in vitro to inactivate aflatoxin B1-epoxide. Carcinogenesis, 2, 299-306.
9.
Gutmann, H.R., Malejka-Giganti, D., Barry, E.J. & Rydell, R.E. (1972). On the correlation between the hepatocarcinogenicity of the carcinogen, N-2-fluorenylacetamide, and its metabolic activation by the rat. Cancer Res., 32, 1554-1561. Heidelberger, C. (1975). Chemical carcinogenesis. Annu. Rev. Biochem., 44, 79-121.
10.
Linsell, C.A. & Peers, F.G. (1977). Field studies on liver cell cancer. In Origins of Human Cancer, eds H. H. Hiatt, J. D. Watson & J. A. Winsten, pp. 549-556. Cold Spring Harbor : Cold Spring Harbor Laboratory.
11.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. & Randall, R.J. (1951). Protein measurement with the Folin phenol reagent . J. Biol. Chem., 193, 265-275.
Lu, A.Y.H., Kuntzman, R. & Conney, A.H. (1976). The liver microsomal hydroxylation enzyme system. Induction and properties of the functional components. Front. Gastrointest. Res., 2, 1-31.
14.
Lutwick, L.I. (1979). Relation between aflatoxins and hepatitis-B virus and hepatocellular carcinoma. Lancet, i, 755-757.
15.
McPherson, G.A.D., Benjamin, I.S., Boobis, A.R., Brodie, M.J., Hampden, C. & Blum-Gart, L.H. (1981). Antipyrine elimination as a dynamic test of hepatic functional integrity in obstructive jaundice . Gut, 23, 734-738.
16.
Omura, T. & Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem., 239, 2370-2378.
17.
Ritchie, J.C., Sloan, T.P., Idle, J.R. & Smith, R.L. (1980). Toxicological implications of polymorphic drug metabolism. In Environmental Chemicals, Enzyme Function and Human Disease, Ciba Foundation Symposium 76 (new series), pp. 219-244. Amsterdam: Excerpta Medica.
18.
Sims, P. (1980). The metabolic activation of chemical carcinogens . Br. Med. Bull., 36, 11-18.
19.
Sultatos, L.G. & Vesell, E.S. (1980). Enhanced drug-metabolizing capacity within liver adjacent to human and rat liver tumors. Proc. Natl Acad. Sci. USA, 77, 600-603.
20.
Tang, T. & Friedman, M.A. (1977). Carcinogen activation by human liver enzymes in the Ames mutagenicity test. Mutat. Res., 46, 387-394.
21.
Wolff, T., Deml, E. & Wanders, H. (1979). Aldrin epoxidation, a highly sensitive indicator specific for cytochrome P-450-dependent mono-oxygenase activities. Drug. Metab. Dispos., 7, 301-305.
