Titre du document / Document title

Induction of micronuclei in metabolically competent rat hepatoma cell lines by the promutagens 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide

Auteur(s) / Author(s)

TAFAZOLI M. ⁽¹⁾ ; VAN HUMMELEN P. ⁽¹⁾ ; KIEFER F. ; KIRSCH-VOLDERS M. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Free univ. Brussels, fac. sci., lab. anthropogenetics, 1050 Brussels, BELGIQUE

Résumé / Abstract

The capability of two rat hepatoma cell lines, H4IIC3/G^- and 2sFou, to detect genotoxicity of xenobiotics, was evaluated in a micronucleus assay. In this system, the cells act as the activation source as well as the target cells for the DNA damage. The study was performed using 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide, as pro-mutagens and mitomycin C as a direct acting mutagen. In both cell lines a significant micronucleus induction was observed after exposure to each test compound, starting from 25 nM for 7,12-dimethylbenz[a]anthracene, 8 μM for benzo[a]pyrene, 0.5 mM for cyclophosphamide and 0.4 μM for mitomycin C. A period of 24 h treatment and 48 h growth was sufficient for induction and expression of micronuclei. The two hepatoma lines behave in a similar way with regard to the pro-mutagen activation. The results obtained in this study with these differentiated hepatoma lines demonstrate that they are metabolically competent to activate the promutagens 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide into their biologically active metabolites as measured by micronucleus induction in our experiments. However, the variable dose responses to 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in some of the repeated experiments, suggest unstable activity of enzymes involved in polycyclic aromatic hydrocarbons metabolism in these cell lines

Revue / Journal Title

Mutagenesis   ISSN 0267-8357   CODEN MUTAEX 

Source / Source

Congrès
United Kingdom Environmental Mutagen Society. Annual meeting N^o18, Hatfield Herts. , ROYAUME-UNI (11/07/1994)
1995, vol. 10, n^o 1, pp. 61-78 (1 p.1/2), pp. 15-21

Langue / Language

Anglais

Editeur / Publisher

Oxford University Press, Oxford, ROYAUME-UNI  (1986) (Revue)

Mots-clés anglais / English Keywords

Rat ; Liver cell carcinoma ; Liver ; Cell line ; Metabolic activation ; Micronucleus ; Mutagenicity testing ; Premutagen ; Polycyclic aromatic compound ; Metabolism ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Rat ; Hépatome ; Foie ; Lignée cellulaire ; Activation métabolique ; Micronucléus ; Test mutagénicité ; Prémutagène ; Benzo[a]anthracène(7,12-diméthyl) ; Benzo[a]pyrène ; Cyclophosphamide ; Composé aromatique polycyclique ; Métabolisme ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Rata ; Hepatoma ; Hígado ; Línea celular ; Activación metabólica ; Micronúcleo ; Prueba mutagenicidad ; Premutágeno ; Compuesto aromático policíclico ; Metabolismo ; Rodentia ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 21345, 35400005934642.0020