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Chapter: Biochemistry: Inborn Errors of Metabolism


Cancer is the second most common cause of death in the world after cardiovascular diseases. Human of all ages develop cancer and wide variety of organs are affected.



o     Cancer is the second most common cause of death in the world after cardiovascular diseases. Human of all ages develop cancer and wide variety of organs are affected.


o     Cancer cells are characterized by three properties: 1) diminished or unrestrained control of growth and cell division; 2) invasion of local tissue; and 3) spread or metastasis to other parts of the body. Cell growth and cell division are regulated by finely tuned control mechanisms.When these processes lose their control, a cell begins to grow uncontrollably. The result is the formation of a mass of cells called a tumour. The overall processes is called neoplasm.


o     The primary event in neoplasm appears to be the alteration in DNA . Most of the tumours are localized without spread and so without risk to the host, they are called benign tumours. Sometimes they start interfering with normal tissues and secreting excessive amount of some hormones or other biologically active substances. These substances are called as tumour markers.


o     Changes in the levels of tumour markers in serum are useful in detecting tumours and cancers. Increase in Ca++ level is seen in multiple myeloma and bone cancer. Elevated levels of alkaline phosphatase is observed in malignancy of bone, liver and carcinoma of bronchus.


o     Tumours become life threatening , when their cells instead of being localized spread throught the body. They become malignant and cause cancer. These cells can spread and invade surrounding tissues or can travel through the blood stream. Development of secondary areas of growth away from the original site of growth is called metastases. Changes in growth properties of cells and their subsequent ability to form malignant tumours are collectively referred to as transformation.


o     Cancers are classified according to the tissue and cell type from which they originate. Those arising from epithelial cells are called carcinomas . Those arising from connective tissue or muscle cells are called as sarcomas. Cancers that do not fit into either of these broad categories include leukemias , lymphomas and cancer of the cells of central nervous system. Nearly 90% of human cancers are carcinomas


Causes of cancer


Agents causing cancer fall into 3 categories: a) radiant energy, b) chemical compounds and c) viruses.


a. Radiant energy: Ultraviolet rays , X-rays andg-rays are mutagenic andcarcinogenic. These rays damage DNA which is presumed to be the basic mechanism of carcinogenicity.

Apart from direct effects on DNA, X - rays and gamma rays cause free radicals to form in tissues which may act as carcinogens.


b. Chemical compounds: A wide variety of organic and inorganic molecules may becarcinogenic.


Examples of organic carcinogens are Benzopyrene, Dimethylbenzanthracene, Dimethylnitrosamine and Aflatoxin B1.

Examples of inorganic carcinogens are arsenic, asbestos, beryllium, cadmium and chromium.


Very few carcinogens interact with DNA directly without further metabolism. These carcinogens are called as direct carcinogens. But many of the carcinogens need prior metabolic activation and the activated ultimate carcinogen can interact with DNA.The ultimate carcinogens are usually electrophiles which readily attack nucleophilic groups in DNA,RNA and proteins.


c. Viruses: Viruses that contain either DNA or RNA as their genome which inducecancer are called as oncogenic viruses. For example Epstein - Barr virus cause Burkitt’s lymphoma and nasopharyngeal carcinoma and Herpes simplex virus cause cancer in the cervix in humans.


Biochemical changes found in tumour cells

The following changes are found in tumour cells


·              Increased synthesis of RNA and DNA.


·              Decreased catabolism of pyrimidines


·              Increased rates of aerobic and anaerobic glycolysis.


Some changes that have been detected at the surface of malignant cells are alteration in transport properties, permeability, surface charge, diminished adhesion, appearance of new antigens, changes of glycolipid constituents and alterations of the oligosaccharide chains of glycoproteins.


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