CANC

ER
-Joanne S. Tonzo

Carcinogens
- are cancer-causing agents
Chemicals (carcinogen)- humans or animals develop
cancer when exposed to them.
Ex. 2-naphthylamine- a potent Carcinogen that causes
bladder cancer. Present in tobacco smoke.
Experiment:
It is feed to laboratory animals and induces a high rate of
bladder cancer. But if it is implanted directly into an

Explanation for Discrepancy

When it is ingested (animals) or inhaled (humans), it passes

through the liver and is metabolized into other chemicals
that are actual causes of cancer.
When It is directly injected in an animals bladder it bypasses
this metabolic activation and so cancer does not arise.
-Carcinogens need metabolic activation before they can
caused cancer they are also called precarcinogens.

Precarcinogens
Most of this are activated by the liver proteins
that are members of Cytochrome P450 enzyme
family.
Cytochrome P450
-Catalyzes oxidation of foreign chemicals (drugs,
pollutants) to make it less toxic and easier to
excrete from the body.
-But in some cases these oxidation reaction
inadvertently concert foreign chemicals into
carcinogens. Know as Carcinogen Activation

DNA Mutations triggered by chemical carcinogen lead to

cancer

During the 1950- Carcinogenic chemicals trigger

DNA mutation.
Ames Test- measuring mutagenic activity.
-uses bacteria culturing, that are a special strain
that cannot synthesize the Amino acid histidine.
-The bacteria are placed in a culture dish
containing a growth medium lacking histidine,
along with chemical being tested for mutagenic

-Normally, bacteria will not grow in the absence of

histidine.
- However, if it is tested with mutagenic chemical,
it will trigger random mutations which might
trigger to restore the ability to synthesize histidine
then it will grow into a visible colony.
Aims test include step in which the chemical is
first incubated with an extract of liver cells to
mimic reactions that normally occur in the liver.
-A strong correlation is observed bet. Chemicals
ability to cause mutations and ability to cause
cancer.

Carcinogenic chemicals inflict DNA Damage;

1.) binding to DNA and disrupting normal base-pairing.
2.) generating crosslinks bet the two strands of double
helix
3.) creating chemical linkage bet adjacent bases
4.) causing breaks in one or both strands.
POLYCYCLIC AROMATIC HYDROCARBONS- binds with
p53ngene and trigger unique mutations in which the
base T is substituted for the base G.

Cancer a multistep process

Initiation- event based mutation on DNA
mutation
Promotion- the initiated cells is stimulated to
proliferate.
Tumor progression- mutations and changes in
gene expression create variant cells exhibiting
enhanced growth rates/other aggressive properties
that give certain cells a selective advantage.

Oncogenes

is a gene whose presence can trigger the

development of cancer.
-Some oncogenes are introduced into cells by
cancer-causing viruses, while others arise from the
mutation of normal cellular genes.
Rous Sarcoma Virus- Causes cancers in chicken,
It has only four genes.

Experiment: Evidence for the existence of

oncogenes in cancer not caused by viruses.
- The DNA isolate from human bladder cancer cells
was introduced into a strain of cultured mouse
cells called 3T3 cells.
-It was stimulated under conditions that stimulate
TRANSFECTION the uptake of the foreign DNA
into the cells and its incorporation into the
chromosomes.
-After being transfected with the cancer cell DNA,
some of the mouse 3T3 cells proliferated
excessively.

The First Human Oncogene was discovered

through gene cloning technique and it is called the
mutant RAS gene, coding for an abnormal form of
Ras.
-It is a protein responsible in growth signaling.
NOTE:
Multiple mutations are usually required to
convert a normal cell into a cancer cell.

Proto-oncogenes are converted into Oncogenes by

several distinct Mechanisms
Q. how do human cancers, most which are not
caused by viruses, come to acquire oncogenes?
A. Oncogenes arise from normal cellular genes
called proto-oncogenes.
PROTO-ONCOGENES
are not bad genes that are simply waiting for
an opportunity to foster the development of

Its term proto-oncogene implies that if and when

the structure or activity of it is disrupted by certain
kind of mutations, the mutant form of the gene can
cause cancer.
The mutation that convert proto-oncogene to
oncogene undergo several distinct mechanisms.

1. Point Mutation involves a single nucleotide substitution

that creates an oncogene coding for an abnormal protein
differing in a single amino acid from the normal protein
produced by the proto oncogene.
2. Gene Amplication - creating multiple gene copies, thereby
leading to excessive production of a normal protein.

3. Chromosomal Translocation moving chromosome

segments from one chromosome to another.
-Fuse two genes together to form an oncogene coding
for an abnormal protein

4. Local DNA rearrangement Such as insertions, deletions,

inversion, and
transpositions can disrupt the structure of
proto-oncogenes and cause them to produce abnormal proteins.
5. Insertional Mutagenesis Occurs when a viral DNA is
integrated into a host chromosome near a proto-oncogene.
-The inserted DNA may stimulate the gene expression of the
proto-oncogene and cause it to produce to much protein.

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