16.2 Toxicogenomics

241

a particular morphology and the ability to form synapses; those attributes that are

strictly correlated with each other need not, of course, be considered separately.

Another difficulty is that a snapshot of the exposome cannot capture the previous

history of exposures, which might well modify the susceptibilities. Clearly, Eq. 16.2

can be used only in rather simple circumstances, but such use should help in deriving

the susceptibility tensor from knowledge of the genome. It should, however, be

emphasized that we are still very far from making such a derivation.

Conversely, features of an ancient environment can be inferred from the DNA

sequences of ancient organisms that are no longer extant. ⁴

Genes partly operate by specifying algorithms for creating metabolic and struc-

tural networks, which support the genome in providing resources for an organism

to adapt to its environment. The redox interface may be critical in the adaptation

process; redox elements are present throughout metabolic systems. ⁵

16.1

Susceptibility to Disease

Nevertheless, steps in the direction indicated by Eq. 16.2 are already being taken,

albeit rather qualitative steps. ⁶ Of particular current interest is the use of epigenomics

to understand disease susceptibility. ⁷ Epigenetic modifications have the advantage

that they can be enacted throughout the lifetime of an organism, from early life

onwards.

16.2

Toxicogenomics

It was known to Pythagoras that the broad bean, Vicia faba, is poisonous to some peo-

ple, ⁸ a condition known as favism and now understood to be due to genetically trans-

mitted glucose-6-phosphate dehydrogenase (G6PD) deficiency. Such phenomena,

well represented by Eq. 16.2, are properly the subject matter of toxicogenomics ⁹—

the consequences of a particular genetic constitution for the metabolic toxicity of

foods and drugs. As Tennant (2002) has pointed out, “toxicology will progressively

develop from predominantly individual chemical studies into a knowledge-based

science in which experimental data are compiled and computational and informatics

tools will play a significant role in deriving a new understanding of toxicant-related

disease”. Of equal importance is the application of mRNA and protein expression

4 Gaucher et al. (2003).

5 Go and Jones (2007).

6 For example, Kunitz (2002).

7 Jirtle and Skinner (2007), Wattacheril et al. (2023).

8 Meletis (2012).

9 Aardema and MacGregor (2002).