The dosing determines mutagenicity of hydrophobic compounds in the Ames II assay with metabolic transformation: Passive dosing versus solvent spiking
作者： Kilian E.C. Smith , Minne B. Heringa , Marijan Uytewaal , Philipp Mayer
DOI: 10.1016/J.MRGENTOX.2012.07.006
关键词:
摘要: a b s t r c The Ames II bacterial mutagenicity assay is new version of the standard test for screening chem- icals genotoxic activity. However, use plastic micro-titer plates has drawbacks in case testing hydrophobic mutagens, since sorptive and other losses make it difficult to control define exposure concentrations, they reduce availability uptake or S9 enzymes. With passive dosing, biocompatible polymer such as silicone loaded with compound acts partitioning source. It compensates any results stable freely dissolved con- centrations. Passive dosing using O-rings was applied measure PAH strains TA98 TAMix - mixture six different detecting differ- ent base-pair substitutions after metabolic activation by S9. Initially, 10 PAHs were tested from saturated O-rings, aiming at levels medium close aqueous solubility. Fluoran- thene, pyrene benzo(a)pyrene mutagenic both TAMix, whereas benz(a)anthracene only. concentration-dependent activity then compared solvent spiking. spiking, nominal concentrations greatly exceeded solubility before observed, due limiting dis- solution kinetics. In contrast, concentration-response curves more reproducible, shifted towards lower several orders magnitude. This study raises fundamental questions about how introduce substances biotransforma- tion, measured not only depends on potency but also its supply, sorption consumption during assay. © 2012 Elsevier B.V. All rights reserved.
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