Biochemestery of cancer

Biochemistry of Cancer

All cancers are multifactorial in origin. They include genetic, hormonal, metabolic, physical, chemical and environmental factors. Most human cancers are spontaneous. Cancer is the second most common cause for death in developed countries, second only to cardiovascular diseases.

Any substance which increases the rate of mutation can also enhance the rate of incidence of cancer. Therefore all carcinogens are mutogens. Examples are X-ray, gamma-ray, ultraviolet ray. Some human cancers are caused by chemicals Examples nitrosamines. These may be introduced into the body by means of (a) occupation (aniline, asbestos), (b) diet (aflatoxins) or (c) lifestyle (smoking).

Action of Chemical Carcinogens

Chemical carcinogens are usually ingested as procarcinogens. They are metabolised in the body, usually in liver, to become the active carcinogen. The enzymes responsible for the activation of procarcinogens are cytochrome P-450 system. On the other hand, direct carcinogens are the ones which interact directly with the target molecules.

Mechanisms of action of chemical carcinogens are:
(a) Carcinogens are generally electrophiles (molecules deficient in electrons); they readily attack nucleophilic (electron rich) groups of DNA.
(b) Carcinogens may bind covalently to cellular DNA.
(c) These changes will lead to DNA alterations, in spite of DNA repair, with increased probability of mutations.

Chemical carcinogens may produce the cancer:
(a) At the site of exposure, e.g. buccal cancer in tobacco chewers, skin cancer in tar workers.
(b) At the site of metabolism, e.g. liver cancer produced by aflatoxin.
(c) At the site of elimination, e.g. bladder cancer in persons working with aromatic dyes.
Four classes of genes are implicated in development of cancer:
1) protooncogenes which are responsible for normal cell growth and differentiation (e.g. K-ras, N-ras).
2) tumor suppressor genes which are involved in recognition and repair of damaged DNA (e.g. P53 gene).