Genotoxicity assessment of aromatic amines and amides in genetically engineered V79 cells.
A genetically engineered V79 cell line expressing rat CYP1A2 and another cell line expressing rat CYP1A2 as well as endogenous acetyltransferase activity, as well as CYP-deficient parental V79 cell lines, were used to assess the genotoxicity of the aromatic amines and amides 2-aminoanthracene, 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline, with chromosomal aberrations and sister chromatid exchanges as the end-points. None of the test compounds showed a clear effect on the frequency of chromosomal aberrations in any cell line used. Sister chromatid exchanges, however, were induced by 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene in the CYP1A2-proficient cells, but not in the CYP1A2-deficient cells. The presence of acetyltransferase activity enhanced the effect of 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene. 4-Acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline did not induce sister chromatid exchanges in the investigated cell lines. The use of cell lines with defined metabolic capabilities seems to be a valuable tool to study specific metabolic pathways important in the activation of procarcinogens.
Rodrigues
A S
AS
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Portugal.
Silva
I D
ID
Caria
M H
MH
Laires
A
A
Chaveca
T
T
Glatt
H R
HR
Rueff
J
J
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D001711:Biotransformation; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology; D005449:Fluorenes / Q000633:toxicity; D005818:Genetic Engineering; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D010088:Oxidoreductases / Q000235:genetics / Q000502:physiology; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000873:Anthracenes; D005449:Fluorenes; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C012177:2-aminofluorene; C006593:2-anthramine; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; C028676:4-acetylaminofluorene