Title of the lecture:
BIOCHEMISTRY OF CANCER
By:
Dr. Salar A. Ahmed
Assistant Professor of Clinical Biochemistry
PhD. In Clinical Biochemistry- Aristotle University of Thessaloniki - Greece
Neoplasm (tumor)
Is an area of tissue whose growth has become
independent of the surrounding tissues).
• The most important types of neoplasm are :
1. Malignant neoplasm = malignant growth = carcinoma
(pre-malignant) = cancer = malignant tumor .
2. Benign neoplasm = benign growth = benign tumor .
Benign neoplasm Malignant neoplasm
Grow Slowly Multiply rapidly
Non infiltrating Infiltrating Diminished or
غير تسلل Unrestrained control of growth
Resembles parent tissues Different from parent tissues
Cells are normal Cells are abnormal and
immortal معمر
املتنقل
Does not spread to distant Metastatic, spread to other parts
sites(non metastatic) of the body & Invasion of local
tissues
The rate of proliferation = that Proliferation exceeds the death
يتجاوز
of cell death rate
Only kills if damaging vital Always kills, if it is not
organs diagnosed early and treated
Cancer
Is a group of diseases involving abnormal cell
growth with the potential to invade or spread to other
parts of the body.
is a long term multistage genetic process.
The first stage is when the DNA is damaged by some
form of carcinogens: مواد مسرطنة
These agents damage or alter DNA (proteins or
enzymes).
Damage to DNA can be by:
1. Covalent binding:
bind covalently to cellular molecules such as DNA,
RNA and proteins
Adinin ,guanine
1. These agents interact with the purines, pyrimidines or
phosphodiester groups of DNA, most common sites of
attack is G
The covalent interactions with DNA can result in several
types of DNA damage ,
this damage can be repaired by the repair system , the
unrepaired damage leads to mutation
additional damage occurs that eventually leads to
chromosome breakdown and rearrangement. This
process produces a new phenotype that loses control
over the process of mitosis. وهذا يفقد السيطرة
Classification of malignant neoplasma
1- The carcinomas:
Are solid tumors that are derived from epithelial tissues
that lines external and internal body surface including
skin, glands, digestive, urinary and reproductive organs
Stomach (gastric adenocarcinoma)
colon( adenocarcinoma of colon)
liver(hepatocelluler carcinoma or hepatoma)
2. The sarcomas:
derived from connective tissues
such as bone, muscle, cartilage, bone marrow and from
cells of lymphatic system
like
bone (osteosarcoma),
plasma cells ( multiple myeloma)
Leukemias and Lymphomas
3- Mixed tissue tumors
derived from tissue that is capable of differentiation
into both epithelial and connective tissue,
Examples
Like ( teratoma) مسخي
Causes of malignancy
its likely that many if not all have a multifactorial
causes).
The principal causes of malignant neoplasm are the
following :
عامل االستحقاق
1- Predisposing factors ( 20%) such as genetic , age ,sex
,race ,diet ,obesity .
2. Environmental factors ,such as :
• Radiation ( radiant energy).
• Chemicals .
• Viruses .
• Hormones .
• Immunological
Radiant energy ( physical)
• Whatever its source
is a wave of energy when this energy
interacts with DNA it causes DNA damage
and mutations that lead to cancer
• Examples:
مهني
leukemia
خطر
may be an
occupational hazard of radiologists, who
are routinely exposed to X-rays,.
Mechanism of carcinogenesis by radiations
1. Direct effect like UV-ray:
Produce damages to DNA which may be as the following
a) Single or double bond strands breaks
b) Cross linking of strands
c) Formation of pyrimidine dimmers بيريميدين مثنوي
d) Elimination of purine/ pyrimidine bases
• Indirect effect:
• X-rays and Y -Rays a part from causing direct damage
to DNA,
• Ionizing radiation have the capacity to displace electrons
from atoms ,thus converting them to ions and cause
generation of free radicals like O2- , H2, OH2-, HOO-,
OH- etc .
• The resultant free radicals, therefore cause chemical
changes within living cell molecules .
Chemical carcinogens:
• A number of chemical substances can cause malignancy,
they are collectively known as chemical
carcinogens(80% of the cancer is caused by the
chemicals) . These`chemicals may be present in
• foods we eat,
• water we drink,
• air we breath,
• the clothing we wear,
• some times in medicines we take and in
• the work place we work
• Chemical carcinogens require long
exposure to produce their carcinogenic
effects which vary with the type and
amount of the carcinogen
Mechanism of action
A- Direct acting carcinogens :
• A few chemical carcinogens like alkylation agents e.g
cyclophosphoamide. can interact directly with the target
molecules DNA, RNA and proteins.
B- Indirect acting carcinogens
Most of the chemicals act as procarcinogens. They are
not chemically reactive.
In the body after metabolism they are converted to
ultimate carcinogens which are highly carcinogenic thus:
Procarcinogen
Proximate(carcinogen)
Ultimate carcinogenic
Highly carcinogenic
Most of the ultimate carcinogens are
electrophiles ( deficient in electrons ) and
thus they can ready react with
nucleophilic (electrons rich) group in
DNA, RNA and various protein
Classification of chemical carcinogens:
According to their occurrence
Chemicals which are used as drags such as exogenous
hormones ( Stilbesterol ),
كبت املناعة
Immunosuppressive drugs, Isoniazed, ,
Cholamphenicol,
Chemicals which cause occupational malignancy such as
Asbestos, CCl4,
Poly cyclic Aromatic Hydrocarbons (PAH),
Aromatic amines, Nitrosamines,
