The process of conversion of a normal cell to malignancy is called carcinogenesis and the agents which cause this are called carcinogens.
Carcinogenesis is a complete process involving interaction of many factors, some of which favour development and others which appear to provide some protection against it.
Cancer can be viewed as a normal process mitosis that in mistimed or misplaced. Proteins such as growth factors, kinases and cyclins partially control the pace of mitosis, and because these, proteins are constructed using genetic information, genes play a role in causing cancer.
Two major classes of genes contribute to causing cancer. ONCOGENES must be activated to cause cancer. TUMOUR SUPPRESSORS, which normally hold mitosis in check, must be inactivated or removed to eleminate control of the cell cycle and initiate cancer.
ONCOGENES
Oncogenes are genes that normally activate cell activates cell division in the wrong time or place, cell, they are normal, essential genes that have undergone a mutation. In its normal nonmutated cancer may result. Oncogenes are not alien to the state, it is a proto-oncogene, a gene that can be transformed into on oncogene.
In 1911. Francis Peyton Rous reported that a virus, later named Rous Sarcoma Virus (RSV), is capable of causing sarcoma, a type of cancer in chickens, RSV is an RNA virus. After the virus infects a cell, it inserts a DNA transcript of its RNA genome, which includes a gene known as sre (for sarcoma gene), into host chromosome, The sre gene is now known to be an oncogene. It is possible that the sre gene is under the control of a viral promotor that has turned it on.
The oncogenes most frequently involved in human cancers belong to the ras gene family. An alteration of only a single nucleotide pair is sufficient to convert a normally functioning ras proto-oncogene to an oncogene. The ras K oncogene is Yound in about 25% of lung cancers, 50% of colon cancer and 90% of pancreatic cancer. The ras N oncogene is associated 'with leukaemias and lymphomas and botch ras oncogenes are frequenty found in thyroid cancers.
Activation of protooncogenes to oncogenes is achieved by at least five mechanism ( pramoter and enhancer insertion, chromosomal translocation, gene amplification, point mutation).
TUMOR SUPPRESSOR GENE
Tumor suppressor gene is so called because it prevents cancer from occurring. Researchers have identified about a half dozen tumour suppressor genes. When these gene malfunction, a tumour results. Tumour suppressor genes are row recognized transe players in the genesis of cancer. The effect on the oncogenes on cell growth has been compared to putting one's foot on the accelerator of an automobile, whereas the action of tumour suppressor prote resembles taking one's foot off the brakes. hard a Important tumour suppressor genes include RBI and P 53, both of which are nuclear phosphoproteins and probably affect the_transcription of genes involved in regulating events in the cell cycle.
A genetic model for colorectal cancer invokes the interplay of tumour suppressor genes and the K-ras oncogene. Mutations in mismatch repair genes have been found to be associated with hereditary and loss of nonpolyposis colon cancer, responsiveness to the growth inhibitory effects of TGF important in development of this type of tumour. A number of cancer susceptibility genes have been isolated. They include RB 1,P 53, BRCA 1, BRCA 2. Tumour progression reflects an instability of the tumour genome, probably due to at least in part to defects In DNA repair systems, activation to additional oncogenes, and inactivation to additional tumour suppressor genes.
The RB tumour suppressor gene was discovered by Alfred Knudson. RB tumour- suppressor gene has now been found to malfunction in cancers of breast, prostate, bladder. Loss of RB tumour suppressor gene through chromosomal deletion is particularly frequent in a type of lung carcinoma.
It is now known that signaling proteins often regulate the transcription of genes whose products are needed for cell division, and this appears to be true of the RB protein. When a particular factor attaches to a receptor, the RB protein is activated. An active RB protein turns off the expression of a proto-oncogene, whose product initiates cell division. Translocations of genes may occur as result of mistakes during mitosis, or they may be caused by carcinogens or viral infection.
Another major tumour-suppressor gene is called P 53, a gene that is more frequently mutated in human cancers than any other known gene. It has been found that the P 53 protein acts an a transcription factor and as such is involved in turning on the expression of a gene called WAP I or Clp 1 The product of this gene is a cell cycle inhibitor. A number of cell proteins combine with the p 53 protein. When a protein combines with p 53, it is hard to tell whether it is activating p 53 or is being activated by p 53. This intricate situation is now being unraveled.
Discovering the normal function of the p 53 gene is a top priority in biomedical research so far, the normal form of gene is implicated in cell cycle control, is cell's expression of other genes, and in several metabolic processes. Understanding p 53 will open the door to understanding many types of of cancer.
CARCINOGENS
While oncogenes and tumour-suppressors play a part in causing cancer, other pOssible causes include certain chemicals, nutrient deficiencies, and radiations.
Direct carcinogens cause cancer when they are applied to fibroblast cells growing in culture. Benzene is an example for this.
Procarcinogens are safe outside the body, but inside they are metabolized to produce intermediate compounds that cause cancer. They include certain organic dyes, cigarettes, nitrites & nitrates used to preserve processed meats.
Promoters are chemicals that make other carcinogens more powerful. They include alcohol, certain hormones and various chemicals in cigrette smoke.
Polycyclic hydrocarbons produce cancer at the site of local application. Aromatic amines like 2- naphthylamine and benzidine cause cancer of urinary bladder. A20-dyes cause liver cancer and amino-fluorenes also cause cancer of liver and urinary bladder. Alkylating agents like mustard gas, methylnitrosourea and nitrosamine and various inorganic compounds like asbestos fibres, arsenic, beryllium, nickel, cadmium, and chromates are all carcinogenic.
Radiation
X-rays, a,ß and Y rays and ultraviolet light all induce tumours in man and animals. While passing through the tissue, these release energy which alters various macromolecules of the cell including nucleic acids. This causes increased of mutations in the irradiated cells.
