Download Environmental Carcinogenesis

Group Number: 2
Britney Porter, Sandra Nguyen, Eduardo Vargas and Samender Singh Randhawa
Environment:
Carcinogenesis:
It is the physical and
biological factors along with
their chemical interactions
that affect an organism
It is literally the creation of cancer. It
is a process by which normal cells are
transformed into cancer cells.
Environmental Carcinogen:
Any of the natural or synthetic substances that can cause cancer. Such
agents may be divided into chemical agents, physical agents, hormones,
and viruses.
What broad category of genes are
involved with carcinogenesis?
• Oncogenes
• Tumor Suppressor Genes
Oncogenes
The first oncogene was discovered
in 1970 and was termed src
An oncogene is a gene that has the
potential to cause cancer.
Activated oncogenes can cause
those cells that ought to die to
survive and proliferate
instead.
This graph (based on the work of E. Sinn et
al, Cell 49:465,1987) shows the synergistic
effect of two oncogenes.
The fraction (%) of transgenic mice without
tumors is shown as a function of age.
Three groups are shown:
• mice transgenic for a
hyperactive myc alone (blue)
• transgenic for ras alone (green)
• transgenic for both myc and ras (red)
Proto- Oncogene
A proto-oncogene is a normal gene that can become an oncogene due to
mutations or increased expression. The resultant protein may be termed an
oncoprotein.
Tumor Suppressor Genes
A code for proteins that signal a cell to stop dividing and leave
the cell cycle.
Unlike the oncogenes that is considered a "go" signal they are a "stop"
signal.
The first tumor suppressor gene was identified by studies of
retinoblastoma, a rare childhood eye tumor.
Another important tumor suppressor is the p53 tumor-suppressor protein encoded by
the TP53 gene. Homozygous loss of p53 is found in 70% of colon cancers, 30–50% of breast
cancers, and 50% of lung cancers. Mutated p53 is also involved in the pathophysiology of
leukemias, lymphomas, sarcomas, and neurogenic tumors. Abnormalities of the p53 gene
can be inherited in Li-Fraumeni syndrome (LFS), which increases the risk of developing
various types of cancers. The mutations can be inherited or can arise de novo early
in embryogenesis or in one of the parent's germ cells.
How would you describe the function of these genes
in normal cells and in cancer cells?
Inactivation of tumor suppressor genes therefore leads to tumor
development by eliminating negative regulatory proteins.
The complete sequence of events required for the development of any
human cancer is not yet known.
As such, p53 has been described as "the guardian of the genome" because of
its role in conserving stability by preventing genome mutation.
In its anti-cancer role, p53 works through several mechanisms:
• It can activate DNA repair proteins when DNA has sustained damage.
• It can induce growth arrest by holding the cell cycle at the G1/S
regulation point on DNA damage recognition (if it holds the cell here for
long enough, the DNA repair proteins will have time to fix the damage
and the cell will be allowed to continue the cell cycle).
• It can initiate apoptosis, the programmed cell death, if DNA damage
proves to be irreparable.
Tumor protein p53
P53 complexed with DNA
Additional questions for further exploration
How can oncogenes and tumor suppressor genes be used to
help prevent cancer?
• Treating problems in tumor suppressor genes is more difficult. It would mean
restoring normal tumor suppressor gene functions, which researchers have
not yet figured out how to do effectively.
• Scientists tried to treat some cancers that have mutations in the
TP53gene by inserting normal TP53genes into viruses and then
trying to infect tumor cells with these viruses. This worked well in
the lab, but not in human studies.
• Increase the amount of p53.
Conclusion
Many researchers are very hopeful about the future of cancer
therapies using oncogenes and tumor suppressor genes, and
this remains a very active area of research. There are many
clinical trials under way today that could lead to better
treatments for many types of cancer.
Why did we choose this question?
We choose this question because the understanding of the genes
that play a role in cancer would give us a good insight of
carcinogenesis. Also we wanted to get a deeper knowledge of the
genetic basis of cancer.
Sources
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1963.tb13433.x/abstract
http://www.ncbi.nlm.nih.gov/pubmed/14643413
http://ask.healthline.com/galecontent/carcinogen
http://cmbi.bjmu.edu.cn/news/0009/23.pdf
http://www.enotes.com/carcinogenesis-reference/carcinogenesis-172934
http://www.cancer.org/Cancer/CancerCauses/GeneticsandCancer/OncogenesandTumorSuppressorGenes/
index
http://www.youtube.com/watch?v=A7bA8b3-Dhg
http://www.broadinstitute.org/education/glossary/tumor-suppressor-gene
http://www.cancer.gov/cancertopics/understandingcancer/cancer/page45