instructing them to construct graphs for each adduct (see
Teacher PPT slide 10). Alternatively, you could divide the
class into small groups and assign each group one adduct
to graph; students could then share their graph with the rest
of the class so that all three graphs can be compared.
(11) Students will need to observe and consider all three graphs
(Figure 3) in order to complete questions in Part II.
(12) Review the answers to the questions in Part II as a class; an
answer key is also available in the online version of the
activity. Collectively, these three adducts can be used to
illustrate to students the marked differences that exist in
how a cell addresses DNA damage:
(a) The short half-life (4 days) of Adduct A is due in part
to this being an unstable adduct.
(b) The long half-life (150 days) of Adduct B is thought to
be due not to active DNA repair but rather to loss due
to cell death and “dilution” due to cell division.
(c) The short half-life (~1 day) of Adduct C is thought to be
due to the fact that there are two DNA repair pathways
that can target and repair this adduct. This built-in
redundancy in the DNA repair mechanism for this particular adduct means that it can be repaired very quickly.
The short half-life means that much shorter time intervals are called for in any study design intended to adequately assess DNA repair; the post-exposure times (2,
4, and 8 weeks) in the featured study were too long in
the case of this particular adduct.
(13) Conclude this activity by discussing the possible consequences of a DNA adduct not being repaired. A DNA
adduct that is not repaired can result in the insertion
of an incorrect base (base-pair substitution) in the opposite DNA strand during DNA replication or in its complementary RNA strand during transcription (see
Teacher PPT slides 15 and 16). Understanding the consequences of an unrepaired DNA adduct implies that a
student has a good grasp of DNA structure and function.
For example, in the case of Adduct B (εG), previous
research has shown that a base pair substitution occurs
~13% of the time, which represents a high mutation rate
(Pottenger et al., 2014).
(14) Students may be interested to learn that in addition to VC,
ethylene oxide and formaldehyde also induce exogenous
DNA adducts that are chemically identical to endogenously formed DNA adducts.
(15) Remind students that knowledge gained about DNA adduct
formation and repair from studies such as these on VC can
be used to understand the mechanisms by which our cells
respond to chemicals in the environment. Emphasize that
in addition to interacting with DNA, chemicals present in
our food, water, and air (and their metabolites) can interact
with other macromolecules (e.g., proteins) in the cell to
impact gene expression (through epigenetic mechanisms)
or metabolism. Studying the impact of exposure to chemicals on our DNA informs risk assessment and the regulation
of chemicals in our environment. Acknowledge that scientists interested in understanding the human exposome are
turning their attention to investigating the impact of low
doses of chemical exposures and of combinations of chemicals on human health. These lines of inquiry are being facilitated by advances in technology and represent an exciting
area of research in the field of exposomics.
Students can complete the worksheet as a formal assessment and/or
they can provide a written summary of the consequences of an unrepaired DNA adduct on gene expression. A key for the worksheet and
graphing activity is included in the Lesson Plan available at https://ie.
Opportunities for Extension
To extend this activity, invite students to conduct independent
research to determine whether there are other chemicals that induce
DNA adducts (some chemicals that induce adduct formation include
polycyclic aromatic hydrocarbons, N-nitrosamines, and aflatoxins).
Students could investigate the mechanisms by which other cancer-causing chemicals damage DNA and the extent to which biomarkers
are being utilized to identify individuals that have been exposed to a
Figure 3. Completed bar graphs help students visualize experimental data (see Teacher PPT slide 13).