Carcinogenesis

Question 1

Define Carcinogenesis

Answer 1

This is the conversion of normal cells to malignant cells by permanent genetic alterations.

Question 2

Define Carcinogen

Answer 2

This are agents that cause the process of carcinogenesis to occur.

Question 3

Define oncogenesis

Answer 3

This is the process of transformation of normal cells to neoplastic cells.

Question 4

Discuss in detail “multiple hypothesis” of carcinogenesis

Answer 4

The process is divided into three stages, the initiation phase, the promotion phase and the progression phase.

Initiation Phase
.Alteration in the genome of the target cell. This genomic alteration is passed on to the progeny
of the target cell.
* The process of initiation:
◦ Is a very rapid event
◦ Is produced in a dose-related fashion
◦ Occurs in a small proportion of the target cell population

Promotion phase
.* This is effected by agents that catalyse biochemical events in normal and initiated cells,
resulting in an altered pattern of gene expression.
* The initiated cells express a new phenotype (appearance), and are regarded as precancerous or
premalignant.

Progression Phase
.Further gene mutations may occur before the malignant phenotype occurs.

Question 5

Classify carcinogens, and list examples of each

Answer 5

This are divided into two groups Intrinsic and extrinsic factors.

Extrinsic factors, this are broken down to three components Physical carcinogens, Chemical carcinogens and viruses.

Chemical Carcinogens:

Chemicals can directly cause cancer or become cancerous after metabolism within cells. They often bind to DNA, disrupting its function.
Examples include polycyclic hydrocarbons from cigarette smoke, aromatic amines causing bladder cancer, vinyl chloride linked to liver angiosarcoma, nitrosamines in gastric cancer, and aflatoxins from Aspergillus flavus in liver cancer.
Inorganic compounds like chrome and nickel also contribute, especially in industries where exposure is common.
Physical Carcinogens:

Irradiation, both therapeutic and ultraviolet, can induce cancer, such as leukemia from therapeutic radiation and skin cancers from UV exposure.
Asbestos exposure is associated with mesothelioma, a type of lung cancer.
Viruses:

Certain viruses, both DNA and RNA types, have been identified as oncogenic. Examples include human papillomavirus (HPV) in cervical cancer, Epstein-Barr virus in Burkitt’s lymphoma and nasopharyngeal carcinoma, hepatitis B virus in liver cancer, human herpesvirus 8 in Kaposi’s sarcoma, and HTLV-1 in adult T-cell leukemia/lymphoma.

Intrinsic factors are divided into four factors, Hormones, Immunological factors, Genetic factors, cellular abnormalities.

Hormones:

Hormonal factors can play a role in cancer development. For instance, estrogen can influence breast and endometrial cancers, while androgen affects prostate cancer.
Immunological Factors:

The immune status of an individual can influence cancer development. Immunosuppression is linked to higher rates of certain malignancies like lymphomas and skin cancers.
Genetic Factors:

Genetic predispositions can increase the risk of cancer. This includes chromosomal syndromes like Down syndrome and Klinefelter syndrome, as well as single-gene abnormalities such as xeroderma pigmentosum and familial adenomatous polyposis coli.
Cellular Abnormalities:

Cancer arises from cellular abnormalities characterized by disturbances in cell proliferation control, differentiation, and interactions with surrounding tissues.
Proto-oncogenes and tumor suppressor genes play crucial roles in regulating cell growth. Mutations or alterations in these genes can lead to oncogene activation, contributing to cancer development.

Question 6

Discuss the regulation of cell proliferation

Answer 6

gene networks, cell cycle checkpoints, and nutrient availability

Question 7

Discuss the functions of proto-oncogens

Answer 7

This are growth promoting genes, they code growth factors, growth factor receptors, signal transducers, nuclear regulatory protein and cell cycle regulators. This behave as dominant genes.

Question 8

Discuss the functions of oncogens

Answer 8

This are autonomous and result in upregulation of the functions or gain of function.
(These alterations may promote cancer development or make cancer more resistant to treatment. Essentially, oncogenes push cells toward uncontrolled growth and survival)

Question 9

Discuss the functions of tumour suppressor genes

Answer 9

This behave as recessive genes meaning that the loss of both copies is required for cancer development.

Question 10

Discuss the functions of DNA repair genes

Answer 10

DNA repair genes play a crucial role in maintaining the integrity and stability of the genome by repairing damage to DNA molecules