title: Carbon black nanoparticles impair acetylation of aromatic amine carcinogens through inactivation of arylamine N-acetyltransferase enzymes.
abstract: Carbon black nanoparticles (CB NPs) and their respirable aggregates/agglomerates are classified as possibly carcinogenic to humans. In certain industrial work settings, CB NPs coexist with aromatic amines (AA), which comprise a major class of human carcinogens. It is therefore crucial to characterize the interactions of CB NPs with AA-metabolizing enzymes. Here, we report molecular and cellular evidence that CB NPs interfere with the enzymatic acetylation of carcinogenic AA by rapidly binding to arylamine N-acetyltransferase (NAT), the major AA-metabolizing enzyme. Kinetic and biophysical analyses showed that this interaction leads to protein conformational changes and an irreversible loss of enzyme activity. In addition, our data showed that exposure to CB NPs altered the acetylation of 2-aminofluorene in intact lung Clara cells by impairing the endogenous NAT-dependent pathway. This process may represent an additional mechanism that contributes to the carcinogenicity of inhaled CB NPs. Our results add to recent data suggesting that major xenobiotic detoxification pathways may be altered by certain NPs and that this can result in potentially harmful pharmacological and toxicological effects.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, 75013, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanfins
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.forename: Florent
authors.initials: F
authors.lastname: Busi
authors.forename: Alain F
authors.initials: AF
authors.lastname: Chaffotte
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues-Lima
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Dupret
mesh_terms: D000107:Acetylation; D001703:Biophysics / Q000379:methods; D002273:Carcinogens / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods*; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000737:chemistry; D053260:Soot / Q000737:chemistry*; D015262:Xenobiotics
chemical_list: D002273:Carcinogens; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D053260:Soot; D015262:Xenobiotics