Cytotoxicity and mutagenicity of 6-aminonicotinamide in Chinese hamster ovary cells.
A strong teratogen-6-aminonicotinamide (6-AN)-was tested for its ability to induce cytotoxicity and mutagenicity in Chinese hamster ovary (CHO) cells. Tests were performed in the presence and absence of a metabolic activation system (S-9 mix). Cytotoxicity was evaluated in CHO cells by the total protein content. The two single-gene mutation systems in CHO cells have been investigated. Both involve evaluating the response of the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus and specific inhibitors of the cellular (Na2+K+)-ATPase using 6-thioguanine and ouabain as selective agents, respectively. From our results, 6-AN showed a higher cytotoxic effect at concentrations over 1 x 10(-1) mg/ml. Cytotoxicity was significantly different with and without S-9 mix. 6-AN was cytotoxic per se, however, when 6-AN was biotransformed, in the presence of S-9 mix no biological activity (cytotoxic) was detected. Non-significant mutagenic activity was detected with 6-AN in the presence and in the absence of the metabolic activation system.
Sanz
F
F
Departmento de Toxicologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Pozuelo
J M
JM
Santa Maria
A
A
D015120:6-Aminonicotinamide / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D005819:Genetic Markers; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D016296:Mutagenesis; D010042:Ouabain / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*; D013866:Thioguanine / Q000494:pharmacology
D005819:Genetic Markers; D011506:Proteins; D013723:Teratogens; D015120:6-Aminonicotinamide; D010042:Ouabain; D007041:Hypoxanthine Phosphoribosyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; D013866:Thioguanine