Appendix: Student Worksheet
Investigating the Exposome: Vinyl Chloride Exposure, DNA Damage & Repair
Vinyl chloride (VC) is an industrial chemical, a component of tobacco smoke, and a byproduct of the microbial breakdown of
perchloroethylene (PERC) and trichlorethylene (TCE) occurring at hazardous waste sites. VC is a known human carcinogen,
and inside the body it is converted into chloroethylene oxide (CEO), which covalently binds to DNA to produce four DNA
adducts (three of these adducts will be investigated during this activity; since their names are not important for this activity,
they will be referred to as Adducts A, B, and C).
1. Define the term exposome.
2. Distinguish between an endogenous chemical exposure and an exogenous chemical exposure.
3. In your own words, define DNA adduct. Why is a DNA adduct considered a form of DNA damage?
4. Research has shown that the DNA adducts produced upon exogenous exposure to VC are identical to those produced by
endogenous exposure to chemicals generated through normal cellular metabolism. Since the adducts that form upon
exposure to VC are identical to adducts that form endogenously, scientists have to have some way to distinguish between
the two in order to better characterize and assess human health risk resulting from exogenous exposure to VC. Propose
how a scientist might do this to determine the impact of exogenous exposure of VC on DNA adduct formation.
Use the data on the back of this sheet to construct bar graphs for Adducts A, B, and C. Once you have completed each
graph, complete the questions below.
5. Observe all three graphs. What conclusions can you draw about endogenous adducts?
6. What conclusions can you draw about adducts induced by exogenous exposure (e.g., inhaled) VC?
7. What happens to the concentration of adducts induced by exogenous exposure to VC over time? Why?
8. Which adduct (A, B, or C) appears to be removed more quickly? How do you know this?
9. It turns out that Adduct B is mutagenic, causing a base pair substitution in the complementary strand of DNA during
replication or in RNA during transcription. Describe the consequences that might result from a base pair substitution
occurring in DNA and RNA.
10. Which adduct (A, B, or C) would be the best biomarker to look for if VC exposure is suspected? Explain your answer.