Proteomic analysis of beryllium-induced genotoxicity in an Escherichia coli mutant model system.
Beryllium is the second lightest metal, has a high melting point and high strength-to-weight ratio, and is chemically stable. These unique chemical characteristics make beryllium metal an ideal choice as a component material for a wide variety of applications in aerospace, defense, nuclear weapons, and industry. However, inhalation of beryllium dust or fumes induces significant health effects, including chronic beryllium disease and lung cancer. In this study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were evaluated using a forward mutant detection system developed in Escherichia coli. In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these results a proteomic study was conducted to identify the proteins regulated by BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully identified 32 proteins being differentially regulated by beryllium and/or MNNG in the E. coli test system. This is the first study to describe the proteins regulated by beryllium in vitro, and the results suggest several potential pathways for the focus of further research into the mechanisms underlying beryllium-induced genotoxicity.
Taylor-McCabe
Kirsten J
KJ
Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Wang
Zaolin
Z
Sauer
Nancy N
NN
Marrone
Babetta L
BL
D001608:Beryllium / Q000494:pharmacology / Q000633:toxicity; D015180:Electrophoresis, Gel, Two-Dimensional; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D029968:Escherichia coli Proteins; D009153:Mutagens; D020543:Proteome; C020711:beryllium sulfate; D001608:Beryllium