Biomaterial Database

Induction of micronuclei in metabolically competent rat hepatoma cell lines by the promutagens 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide. 1995

M Tafazoli, and P Van Hummelen, and F Kiefer, and M Kirsch-Volders

Laboratory for Anthropogenetics, Faculty of Sciences, Free University of Brussels.

The capability of two rat hepatoma cell lines, H4IIEC3/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 microM for benzo[a]pyrene, 0.5 mM for cyclophosphamide and 0.4 microM 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.

UI	MeSH Term	Description	Entries
D008114	Liver Neoplasms, Experimental	Experimentally induced tumors of the LIVER.	Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008297	Male		Males
D009153	Mutagens	Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.	Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D011355	Prodrugs	A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.	Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D003520	Cyclophosphamide	Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.	(+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001564	Benzo(a)pyrene	A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.	3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015127	9,10-Dimethyl-1,2-benzanthracene	Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen.	7,12-Dimethylbenzanthracene,7,12-Dimethylbenz(a)anthracene,7,12 Dimethylbenzanthracene