1(a). CONCEPTUAL
FOUNDATIONS
Created Jan 11, 2020 1137 AM
Tags
Updated Jan 16, 2020 420 PM
Lodish: Molecular Cell Biology - Chapter 24
The Origin and Development of Cancer
What is cancer?
cancer is defined as the continuous uncontrolled growth of cells
a tumour is any abnormal proliferation of cells
benign tumours - the tumours stay confined to the original location
malignant tumours - the tumours are capable of invading surrounding
tissue or invading the entire body
tumours are classified as to their cell type and can arise from any cell type
in the body
examples:
carcinoma (epithelial)
sarcoma (bone and soft tissues)
leukemia (blood-forming tissue of bone marrow)
lymphoma (lymphocytes)
melanoma (melanocytes)
Solid Tumour Incidence and Death Rate
most tumours are carcinomas which arise from epithelial linings
causes 80% of cancer-related deaths
lung and pancreatic cancer have much lower survival rates as opposed to
other cancers
1(a). CONCEPTUAL FOUNDATIONS 1
, geographic variation in cancer incidence
people in different areas of the world are more susceptible towards
different cancers
this is due to the differences in genetic make-up
Carcinogens
1(a). CONCEPTUAL FOUNDATIONS 2
, Carcinogens are substances which are capable of causing cancer in living
tissue, and there are several:
ionising radiation
X-rays
UV light
chemicals
benzo(a)pyrene (from coal tar or cigarette smoke) SEE BELOW
alcohol
tris(2,3-dibromopropyl)phosphate (flame retardant)
furylfuramide (antibacterial food additive)
virus infection
papilloma virus - possible cervical cancer
hepatitis B and C - liver cancer
hereditary predisposition
some families are more susceptible to certain cancers
eg. BRCA BReast CAncer) gene has been found to impact the chances
of developing breast cancer but do not actually case the cancer
Chemical Carcinogens
These are chemicals that are reasonably anticipated to cause cancer in
humans
thousands of chemicals have been identified as carcinogens
eg. benzene, beryllium, asbestos, arsenic
the range of chemical structures is very broad
they are classified into two categories:
direct-acting
these modify the Nitrogen and Oxygen atoms in DNA bases, which
cases the base pairing to change and introduce mutations
this is seen in cystic fibrosis patients
eg. ethyl methane sulphonate, dimethyl sulphate, nitrogen mustards
1(a). CONCEPTUAL FOUNDATIONS 3
, indirect-acting
these are generally unreactive, water-insoluble compounds
eg. animal cell P450 enzymes add hydroxyl groups to chemicals
(such as insecticides and therapeutic drugs) to solubilise them for
excretion, which can turn them into carcinogens
Benzo(a)pyrene as a Pro-Carcinogen
Benzo(a)pyrene can be found in coal tar, tobacco smoke and many foods such
as grilled meat
cigarette smoke contains about 60 carcinogens, one of which is
benzo(a)pyrene and they can induce mutations in different genes
how does it happen?
60% of lung cancers have inactivating mutations in the P53 gene, which
is a major tumour suppressor gene
benzo(a)pyrene, which is a pro-carcinogen, then can undergo P450
mediated activation in the lungs
this causes nucleotide conversion
the P53 mutational patterns vary in frequency:
1(a). CONCEPTUAL FOUNDATIONS 4
FOUNDATIONS
Created Jan 11, 2020 1137 AM
Tags
Updated Jan 16, 2020 420 PM
Lodish: Molecular Cell Biology - Chapter 24
The Origin and Development of Cancer
What is cancer?
cancer is defined as the continuous uncontrolled growth of cells
a tumour is any abnormal proliferation of cells
benign tumours - the tumours stay confined to the original location
malignant tumours - the tumours are capable of invading surrounding
tissue or invading the entire body
tumours are classified as to their cell type and can arise from any cell type
in the body
examples:
carcinoma (epithelial)
sarcoma (bone and soft tissues)
leukemia (blood-forming tissue of bone marrow)
lymphoma (lymphocytes)
melanoma (melanocytes)
Solid Tumour Incidence and Death Rate
most tumours are carcinomas which arise from epithelial linings
causes 80% of cancer-related deaths
lung and pancreatic cancer have much lower survival rates as opposed to
other cancers
1(a). CONCEPTUAL FOUNDATIONS 1
, geographic variation in cancer incidence
people in different areas of the world are more susceptible towards
different cancers
this is due to the differences in genetic make-up
Carcinogens
1(a). CONCEPTUAL FOUNDATIONS 2
, Carcinogens are substances which are capable of causing cancer in living
tissue, and there are several:
ionising radiation
X-rays
UV light
chemicals
benzo(a)pyrene (from coal tar or cigarette smoke) SEE BELOW
alcohol
tris(2,3-dibromopropyl)phosphate (flame retardant)
furylfuramide (antibacterial food additive)
virus infection
papilloma virus - possible cervical cancer
hepatitis B and C - liver cancer
hereditary predisposition
some families are more susceptible to certain cancers
eg. BRCA BReast CAncer) gene has been found to impact the chances
of developing breast cancer but do not actually case the cancer
Chemical Carcinogens
These are chemicals that are reasonably anticipated to cause cancer in
humans
thousands of chemicals have been identified as carcinogens
eg. benzene, beryllium, asbestos, arsenic
the range of chemical structures is very broad
they are classified into two categories:
direct-acting
these modify the Nitrogen and Oxygen atoms in DNA bases, which
cases the base pairing to change and introduce mutations
this is seen in cystic fibrosis patients
eg. ethyl methane sulphonate, dimethyl sulphate, nitrogen mustards
1(a). CONCEPTUAL FOUNDATIONS 3
, indirect-acting
these are generally unreactive, water-insoluble compounds
eg. animal cell P450 enzymes add hydroxyl groups to chemicals
(such as insecticides and therapeutic drugs) to solubilise them for
excretion, which can turn them into carcinogens
Benzo(a)pyrene as a Pro-Carcinogen
Benzo(a)pyrene can be found in coal tar, tobacco smoke and many foods such
as grilled meat
cigarette smoke contains about 60 carcinogens, one of which is
benzo(a)pyrene and they can induce mutations in different genes
how does it happen?
60% of lung cancers have inactivating mutations in the P53 gene, which
is a major tumour suppressor gene
benzo(a)pyrene, which is a pro-carcinogen, then can undergo P450
mediated activation in the lungs
this causes nucleotide conversion
the P53 mutational patterns vary in frequency:
1(a). CONCEPTUAL FOUNDATIONS 4
