The N-acetoxy and N-hydroxy derivatives of trans-4-acetylamino-stilbene (AAS) were demonstrated to induce gene mutations at the hgprt locus and to be cytotoxic in V79 cells. These cells deacetylated AAS. Paraoxon inhibited the deacetylation of AAS by more than 99% and reduced the mutagenicicity and cytotoxicity of N-hydroxy-ASS and N-acetoxy-AAS to about one-tenth. Hence, deacetylated metabolites, formed by the target cells, were important for the observed biological effects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- AAF:
-
2-acetylaminofluorene
- AAS:
-
trans-4-acetylaminostilbene
- AS:
-
trans-4-aminostilbene
References
ANDERSON, R.A., ENOMOTO, M., MILLER, E.C. and MILLER, J.A. (1964). Carcinogenesis and inhibition of the Walker 256 tumor in the rat by trans-4-acetylaminostilbene, its N-hydroxy-metabolite, and related compounds. Cancer Res. 24:128–143.
BRANDT, E., HEYMANN, E. and MENTLEIN, R. (1980). Selective inhibition of rat liver carboxylesterases by various organophosphorus diesters in vivo and in vitro. Biochem. Pharmacol. 29:1927–1931.
GAUGLER, B.J.M. and NEUMANN, H.-G. (1979). The binding of metabolites from aminostilbene derivatives to nucleic acids in the liver of rats. Chem.-Biol. Interact. 24:355–372.
GLATT, H.R. and OESCH, F. (1985). Activation of N-acetoxy- and N-hydroxy-2-acetylaminofluorene to mutagenic and cytotoxic metabolites by V79 Chinese hamster cells. Mutat. Res. 149:265–269.
GLATT, H.R., OESCH, F. and NEUMANN, H.-G. (1980). Factors responsible for the metabolic formation and inactivation of bacterial mutagens from trans-4-acetylaminostilbene, Mutat. Res. 73:237–250.
HOLME, J.A. and SøDERLUND, E.J. (1984). Modulation of genotoxic and cytotoxic effects of aromatic amines in monolayers of rat hepatocytes. Cell Biol. Toxicol. 1:95–110.
IRVING, C.C. (1966). Enzymatic deacetylation of N-hydroxy-2-acetylaminofluorene by liver microsomes. Cancer Res. 26:1390–1396.
KRIEK, E. (1972). Persistent binding of a new reaction product of the carcinogen N-hydroxy-N-2-acetylaminofluorene with guanine in rat liver DNA in vivo. Cancer Res. 32:2042–2048.
KRIEK, E. (1974). Carcinogenesis by aromatic amines. Biochim. Biophys. Acta 355:177–203.
MAHER, V.M., HEFLICH, R.H. and McCORMICK, J.J (1981). Repair of DNA damage induced in human fibroblasts by N-substituted aryl compounds. Nat. Cancer Inst. Monographs 58:217–222.
METZLER, M. and NEUMANN, H.-G. (1971). Zur Bedeutung chemisch-biologischer Wechselwirkungen für die toxische und krebserzeugende Wirkung aromatischer Amine, III. Synthese und Analytik einiger Stoffwechselprodukte von trans-4-Dimethylaminostilben, cis-4-Dimethylaminostilben und 4-Dimethylaminobibenzyl, Tetrahedron 27:2225–2246.
NEUMANN, H.-G. (1983). Role of extent and persistence of DNA modifications in chemical carcinogenesis by aromatic amines. Recent Results in Cancer Research, Vol. 84, Springer-Verlag Berlin-Heidelberg, pp. 77–89.
POIRIER, M.C., WILLIAMS, G.M. and YUSPA, S.H. (1980). Effects of culture conditions, cell type, and species of origin on the distribution of acetylated and deacetylated deoxyguanosine C-8 adducts of N-acetoxy-2-acetylaminofluorene. Mol. Pharmacol. 18:581–587.
SCHUT, H.A.J., WIRTH, P.J. and THORGEIRSSON, S.S. (1978). Mutagenic activation of N-hydroxy-2-acetylaminofluorene in the Salmonella test system: the role of deacetylation by liver and kidney fractions from mouse and rat. Mol. Pharmacol. 14:682–692.
STAIANO, N., ERICKSON, L.C., SMITH, C.L., MARSDEN, E. and THORGEIRSSON, S.S. (1983). Mutagenicity and DNA damage induced by arylamines in the Salmonella/hepatocyte system. Carcinogenesis 14: 161–167.
THORGEIRSSON, S.S., SCHUT, H.A.J., TAIANO, N., WIRTH, P.J. and EVERSON, R.B. (1981). Mutagenicity of N-substituted aryl compounds in microbial systems. Nat. Cancer Inst. Monographs 58: 229–236.
WESTRA, J.G., KRIEK, E. and HITTENHAUSEN, H. (1976). Identification of the persistently bound form of the carcinogen N-acetyl-2-aminofluorene to rat liver DNA in vivo. Chem. Biol. Interact. 15:149–164.
ZIELINSKI, E. and NEUMANN, H.-G. (1983). The role of hydroxamic acid esters for the genotoxic effects of trans-4-acetylaminostilbene. Abstracts of the VIIth Meeting of the European Association for Cancer Research, 1983.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Glatt, H., Oesch, F. & Neumann, HG. V79 Chinese hamster cells deacetylate Trans-N-acetoxy-4-acetylaminostilbene and Trans-N-hydroxy-4-acetylaminostilbene to mutagenic and cytotoxic metabolites. Cell Biol Toxicol 2, 213–221 (1986). https://doi.org/10.1007/BF00122690
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00122690