worksheet and answer key is available at https://ie.unc.edu/dna-epigenetics/. The PPT slide set is available at https://ie.unc.
• Prepare students for this activity: they should have a basic
understanding of DNA structure and function and the fundamentals of gene expression.
• Make copies of the double-sided student worksheet (see Lesson
Plan and Appendix), one per student.
(1) Prompt students to consider that completing the sequencing
of the human genome in 2003 led to a revolution in other
“-omics” sciences and technologies to better understand the
interactions that take place between our genes, our proteins,
and our environment and to elucidate causes of human
disease. Our environment includes tens of thousands of
chemicals that we are exposed to throughout our lifetime,
starting in utero; thus, an investigation of gene–environment
interactions must include chemical exposures.
(2) Introduce students to the concept of the exposome (see
Teacher PPT slide 2), which was first introduced in 2005
(Wild, 2005) and refers to an individual’s lifetime exposure to chemicals from the environment coupled with
exposure to chemicals formed inside our cells as a consequence of metabolic processes. Your students may have
never considered that their very own cells produce
chemicals, some of which are toxic.
(3) Distinguish between endogenous and exogenous exposure
to chemicals and discuss the relevance in relation to chemical exposure (improved risk assessment, cancer, etc.).
When evaluating the toxicity of chemicals in our environment, scientists need to be aware if these toxic effects can
Table 1. Characterization of the three adducts that are the focus of this activity. Each adduct is a
modified nitrogenous base.
DNA Adducta Abbreviation Action Half-life (Liver)
7-(2-oxoethyl)guanine (Adduct A) 7-OEG Lacks miscoding properties and is removed
from DNA by chemical depurination
N2,3-ethenoguanine(Adduct B) εG Promutagenic activity during DNA synthesis 150 days
1,N6-ethenodeoxyadenosine (Adduct C) εdA Promutagenic activity during DNA synthesis ~1 day
aFor the purpose of this activity, the scientific names of these adducts are not important. 7-OEG will be referred to as Adduct A; εG will be referred to as Adduct B;
and εdA will be referred to as Adduct C on the student worksheet.
Figure 2. Scientists can use stable-isotope labeled (13C2)-VC and track its incorporation into DNA adducts. VC-induced adducts
will have stable-isotope labels; endogenous adducts will not. In this study, the formation of VC-induced DNA adducts was
examined in rat liver tissue, the primary site of VC metabolism. Students should observe that the number of endogenous DNA
adducts do not significantly change over time, as would be expected from an endogenous mutagenic chemical; there are steady-state amounts of endogenous DNA damage in our cells as new adducts are formed and repaired continuously. Students will
observe greater adduct formation in response to exogenous exposure to (13C2)-VC and a variation in the extent to which each
adduct gets repaired.