Sigma xi slideshow

1. Can Flavonoids Cause DNA Damage
and Chromosomal Translocations
Similar to Those Seen in Leukemia?
By: Mimi Ughetta

2.  Chromosome Translocation: DNA of two chromosomes is
damaged and break before rejoining incorrectly to each
other. The genes at the joints are incorrect and cause
disease like leukemia.
 Etoposide is a known toxin and is known to cause DNA
damage and leukemia.
 Flavonoids are in the natural diet and high doses in soy
products and energy drinks. They also have a similar
phenolic ring structure to Etoposides, so Flavonoids are
thought to also cause the same damage that leads to
leukemia.
Background:

3.  I hypothesized flavonoid compounds in our
environment and diet can cause DNA damage and
chromosomal translocations joining chromosome 9
and chromosome 11 in certain blood cells, which leads
to leukemia.
Hypothesis:

4. 1. Blood stem cells were engineered with GFP reporters on
chromosome 9 and 11 before exposed to 100microM etoposide,
flavonoids (genistein, quercetin, myricetin, luteolin), industrial
toxins (benzoquinone), or other phenolic ring compounds
(vitamin A) for 1 hr.
2. DNA was isolated from GFP+ colonies, and PCR was performed on
each using one DNA primer matching sequence on both
chromosomes 11 and 9. (Only when primers are on the same
chromosome, and the translocation occurred, will there be PCR+)
3. PCR DNA was ligated into plasmid vectors and transformed into
bacteria.
Research Methods:

5. 4. The DNA fragments from plasmid DNA vectors were
isolated from the bacterial transformants.
5. The samples were sent to a company that reads the DNA
sequences. This procedure showed the joining of
chromosome 11 and 9, through a process called endjoining
ligation repair, which is seen in leukemia patients.
Methods Continued:

6. Results:
associated with non-MLL-rearranged leukemias, and dipyone, which is not a known topo
II inhibitor generated none and one GFP+ colonies respectively at a high dose. Both these
compounds are believed to have distinct mechanisms of action, different from the other
topo II inhibitors used in this study.
Figure 23: A bar chart representing the relative frequencies of appearance of GFP+
 When blood cells were
exposed to eptoposides,
flavonoids, industrial
toxins, or other phenolic
ring compounds, only cells
exposed to etoposides
and flavonoids produced
GFP+ colonies. This means
that cells exposed to
etoposide or flavonoids
underwent DNA damage
and chromosomal
translocations that led to
leukemia.

7.  The company that read the
DNA samples sequenced them.
The sequences showed the
joining of chromosome 11 and
9 in the blood cells I tested on
similar to leukemia patients, by
a process called endjoining
ligation repair. Therefore, we
conclude genistein and
quercetin cause the same type
of DNA damage and repair
seen in leukemia.
Results:

8.  The flavonoids, genistein and quercetin, are in many
energy drinks and sold in health food stores. Despite
being good in small doses, this shows a high flavonoid
diet may increase the risk for leukemia because these
flavoidnoids cause DNA damage and chromosomal
translocations like in leukemia. Moreover, the repair
of DNA damage is by endjoining, which is the same
pathway in leukemia.
Conclusions: