Arylamines suppress their own activation and that of nitroarenes in V79 Chinese hamster cells by competing for acetyltransferases.
The effect of 2-aminofluorene (2-AF) on the toxicity of 2-aminoanthracene (2-AA) and 1,6-dinitropyrene (1,6-DNP) was studied in N-acetyltransferase-proficient V79-NHr1A2 cells genetically engineered for the expression of cytochrome P4501A2, and in wild-type V79-NH cells. 2-AA inhibited the growth of V79-NHr1A2 cells and induced the formation of micronuclei at concentrations of 0.1 to 1.0 microM, but was virtually without toxic effects at a concentration of 10 microM. Addition of 2-AF protected against the cytotoxic and genotoxic effects elicited by low concentrations of 2-AA. Half-maximum protection was observed at 0.2 to 0.5 microM 2-AF. The arylamine also prevented the cytotoxicity caused by 1,6-DNP in V79-NH cells and completely suppressed the formation of 1-acetylamino-6-nitropyrene from 1,6-DNP in these cells. The results indicate that arylamines and related N-hydroxyarylamines are substrates for the same acetyltransferase in V79-NH cells. In consequence, arylamines are capable of suppressing the activation of their proximate cytotoxic and genotoxic products in these cells and, presumably, in vivo.
Kiefer
F
F
Institut für Toxikologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany.
Cumpelik
O
O
Reen
R
R
Doehmer
J
J
Wiebel
F J
FJ
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D001667:Binding, Competitive; D016466:CHO Cells; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004336:Drug Antagonism; D005449:Fluorenes / Q000494:pharmacology*; D009153:Mutagens / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity*
D000873:Anthracenes; D002273:Carcinogens; D005449:Fluorenes; D009153:Mutagens; D011721:Pyrenes; C012177:2-aminofluorene; C033309:1,6-dinitropyrene; C006593:2-anthramine; D000123:Acetyltransferases