103
Interactions between chemicals and living organisms are governed by toxicokinetic and toxicodynamic processes [37], and contemporary studies in both fields
rely heavily on mass spectrometry [38]. Toxicokinetics describes uptake, biotransformation, distribution, and excretion of a chemical by an organism, also referred to
as absorption, distribution, metabolism, and excretion (ADME) processes [39, 40].
Toxicodynamics looks at the actions of a chemical or its metabolite, carried out at
the target sites where toxicity becomes manifested [32]. Such actions could include,
for example, DNA adduct formation [41], oxidation of membrane lipids [9], or
binding to a nuclear receptor, which in turn could trigger gene or protein expression
changes and metabolite alterations [8, 40, 42–44].
Information on effective internal organismal or tissue concentrations of chemicals and their transformation products is important for toxicokinetic modeling [39]
and can be obtained with the same approaches as applied to environmental compartments [14, 16, 44]. Taking samples at different time points, performing depuration
experiments, or carrying out non-targeted or targeted metabolite screening allows
constructing time-resolved profiles of chemical uptake, biotransformation, and
excretion [39, 40, 45, 46]. MS has also been instrumental in obtaining information
that sheds light on the internal distribution of chemicals. This can be done by measuring chemical contents in the dissected body parts or by using MALDI imaging to
decipher chemical location on tissue sections, e.g. from zebrafish larvae [39, 46].
For example, a study of the internal distribution of cocaine in zebrafish larvae
showed that cocaine was not only located at the target site, the brain, but also in the
melanin-containing eye of the larvae [39], providing a better understanding of the
differences in responses to psychoactive drugs observed in mammals and zebrafish
larvae [46].
With regard to toxicodynamics, MS can provide data on gene expression and
cellular signaling cascades, for example through looking at proteins (proteomics)
and metabolites (metabolomics) [47]. The universal nature of cellular (macro)molecules and metabolites allows applying similar methods when studying organisms
across the whole animal kingdom, from microorganisms [9, 43, 48] to mussels [8]
to fish [29, 49–51] and other organisms [16, 38, 52].
Figure 6.7 shows that mRNA levels (studied by transcriptomics) are fast reacting
and hence reflect the organism’s response to the immediate challenge by a specific
stressor. Changes in the proteins often reflect the more downstream changes, which
could be delayed in time and are often observed to converge in a general stress
response [54]. The metabolome is often as fast reacting as the transcriptome and
thus can be seen as a fingerprint of the state of a cell, tissue or organism at a given
moment [55, 56]. The study of metabolomics is rapidly establishing itself in ecotoxicological research [52], also because its analytical pipelines are often similar to
untargeted environmental chemical analysis [16, 57].
Both global (data-dependent acquisition) and targeted (MRM) techniques can be
used to investigate the proteome and metabolome. Multidimensional Protein
Identification Technology (MudPIT), also referred to as global proteomics, allows
the simultaneous characterization of several thousands of proteins as well as their
alterations in response to toxicants [10]. This can be done for well-studied model
6 Mass Spectrometry in Ecotoxicology
Interactions between chemicals and living organisms are governed by toxicokinetic and toxicodynamic processes [37], and contemporary studies in both fields
rely heavily on mass spectrometry [38]. Toxicokinetics describes uptake, biotransformation, distribution, and excretion of a chemical by an organism, also referred to
as absorption, distribution, metabolism, and excretion (ADME) processes [39, 40].
Toxicodynamics looks at the actions of a chemical or its metabolite, carried out at
the target sites where toxicity becomes manifested [32]. Such actions could include,
for example, DNA adduct formation [41], oxidation of membrane lipids [9], or
binding to a nuclear receptor, which in turn could trigger gene or protein expression
changes and metabolite alterations [8, 40, 42–44].
Information on effective internal organismal or tissue concentrations of chemicals and their transformation products is important for toxicokinetic modeling [39]
and can be obtained with the same approaches as applied to environmental compartments [14, 16, 44]. Taking samples at different time points, performing depuration
experiments, or carrying out non-targeted or targeted metabolite screening allows
constructing time-resolved profiles of chemical uptake, biotransformation, and
excretion [39, 40, 45, 46]. MS has also been instrumental in obtaining information
that sheds light on the internal distribution of chemicals. This can be done by measuring chemical contents in the dissected body parts or by using MALDI imaging to
decipher chemical location on tissue sections, e.g. from zebrafish larvae [39, 46].
For example, a study of the internal distribution of cocaine in zebrafish larvae
showed that cocaine was not only located at the target site, the brain, but also in the
melanin-containing eye of the larvae [39], providing a better understanding of the
differences in responses to psychoactive drugs observed in mammals and zebrafish
larvae [46].
With regard to toxicodynamics, MS can provide data on gene expression and
cellular signaling cascades, for example through looking at proteins (proteomics)
and metabolites (metabolomics) [47]. The universal nature of cellular (macro)molecules and metabolites allows applying similar methods when studying organisms
across the whole animal kingdom, from microorganisms [9, 43, 48] to mussels [8]
to fish [29, 49–51] and other organisms [16, 38, 52].
Figure 6.7 shows that mRNA levels (studied by transcriptomics) are fast reacting
and hence reflect the organism’s response to the immediate challenge by a specific
stressor. Changes in the proteins often reflect the more downstream changes, which
could be delayed in time and are often observed to converge in a general stress
response [54]. The metabolome is often as fast reacting as the transcriptome and
thus can be seen as a fingerprint of the state of a cell, tissue or organism at a given
moment [55, 56]. The study of metabolomics is rapidly establishing itself in ecotoxicological research [52], also because its analytical pipelines are often similar to
untargeted environmental chemical analysis [16, 57].
Both global (data-dependent acquisition) and targeted (MRM) techniques can be
used to investigate the proteome and metabolome. Multidimensional Protein
Identification Technology (MudPIT), also referred to as global proteomics, allows
the simultaneous characterization of several thousands of proteins as well as their
alterations in response to toxicants [10]. This can be done for well-studied model
6 Mass Spectrometry in Ecotoxicology