Cell uptake and DNA adduct formation of the 2-amino-3 methyl-imidazo (4,5-f) quinoline in human enterocytes and chick embryo liver cells.
The compound 2-amino-3-methyl-imidazo(4,5-f)quinoline (IQ) is a powerful mutagenic compound that can induce tumours in different rat and murine target organs (liver, forestomach and small and large bowel). The ability of mutagenic IQ to form adducts to human embryonic enterocyte DNA (intestine 407 cell lines ATCC) has been studied, considering the DNA extracted from the cells and DNA of the in vitro-cultured cells. The activation with the rat hepatic microsomial fraction S9 plays an important role not only in DNA binding, but also in the uptake of IQ by the enterocytes. In the presence of S9 mix, the DNA adduct formation increases with the incubation time; in the absence of metabolic activation, the binding does not occur. Parallel experiments were carried out for comparison on chick embryo hepatocytes; for these cells, the metabolic activation with S9 mix is not as critical as for enterocytes in IQ uptake and DNA binding.
Pistolesi
R
R
Department of Cellular and Molecular Biology, University of Perugia, Italy.
Giammarioli
M
M
Pezzetti
F
F
Bodo
M
M
Trotta
F
F
Morozzi
G
G
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000196:embryology; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000493:pharmacokinetics*; D011485:Protein Binding; D011804:Quinolines / Q000493:pharmacokinetics*; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D018736:DNA Adducts; D009153:Mutagens; D011804:Quinolines; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA