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BIOCHEMISTRY OF CANCER

1. Write a note on agents which bring abot carcinogenesis. !on No" #$1$#. E%&'ain the (echanis(s in"o'"e) in carcinogenesis. !on Ma* #$1$+. Oncogenes. M,R Ag #$$-. Mtagens M,R Feb #$1#

/. Carcinogenic "irs. M,R Ag #$$0. Na(e two t(or s&&ressor genes an) the (a'ignanc* that is s&eci2ca''*

associate) with abnor(a'ities in each o3 these genes. M,R Feb #$14. Write a note on t(or s&&ressor genes. !on No" #$1$-. Carcinogenic "irs.

ETIO5O,Y OF CANCER6

1. All cancers originate from one aberrant cell. During surveillance by the immune

system, these aberrant cells are usually destroyed. As age advances, the probability of 

the incidence of cancer is increased.2. Cancers are multifactorial in origin. They include genetic, hormonal, metabolic,

physical, chemical and environmental factors.

M7TA,ENS61. Any substance hich increases the rate of mutation can also enhance the rate of

incidence of cancer. Therefore all carcinogens are mutogens.#. !"amples are Chemicals, #$ray, gamma$ray, ultraviolet ray etc.

CHEMICA5 CARCINO,ENS6

C'assi2cation6

1. %rganica. Dimethyl ben&anthracene,b. 'en&o pyrene,c. Dimethyl nitrosamine

2. (norganica. Arsenic,b. Cadmium

3. %ccupation) Asbestos, ben&ene.*. Diet) A+ato"in '. Drugs)

a. -ormones) diethylstibesterol.b. Chemotherapeutic agents

. /ife style) cigarette smo0ing.

Mechanis( o3 action6

1. Chemical carcinogens act c('ati"e'*. They bind to purines, pyrimidines and

phosphodiesterase bonds of DA causing unrepairable damage. The chemical

carcinogens freuently cause mutations of DA hich may nally lead to the

development of cancer, hence they are regarded as mutagens.2. A(es assa*) This is a laboratory test to chec0 the carcinogenecity of chemicals.

4utant strain of 5almonella typhimurium can not synthesi&e histidine. Addition of

chemical carcinogens causes reverse mutation restoring the ability of the bacteria to

synthesi&e histidine. 'y detecting this reverse mutation in 5almonella in the colonies

of agar plates, the chemical mutagens can be identied.3. !ro(oters) 4ost carcinogens reuire promoters for the production of a cancer.

'en&opyrene applied on s0in does not produce cancer. Croton oil application also does

not lead to s0in cancer. 'ut hen ben&opyrene application is folloed by croton oil,

tumor is developed. (n this case, croton oil is termed as the promoter.

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*. !rogression) Development of familial adenomatous polyposis is a good e"ample for

multistep progression. 4utations in the A7C gene are inherited from parents. 'y the

time the patient becomes adult, there ill progress to form adenomas. urther

mutation lead to the development of malignancy.. Chemical carcinogens may produce the cancer) 9a: At the sit of e"posure, e.g. buccal

cancer in tobacco cheers, s0in cancer in tar or0ers. 9b: At the site of metabolism,

e.g. liver cancer produced by a+ato"in. 9c: At the site of elimination, e.g. bladder

cancer in persons or0ing ith aromatic dyes.

I(&ortant che(ica' carcinogens6

1. A+ato"ins) They are a group of chemically related compounds synthesised by the

fungi, Aspergillus +avus. The mould gros on rice, heat and groundnut, hen 0ept in

damp conditions. The fungi may gro in cattle fodder, hich may enter into human

body through the co;s mil0. A+ato"ins are poerful carcinogens, hich produce

hepatomas .2. Cigarette) /ung cancer is associated ith the habit of cigarette smo0ing. Cigarette

contains many carcinogens, the most important group being ben&o9a:pyrenes. %ther

important deleterious substances in cigarette smo0e are nicotine, carbon mono"ide,

nitrogen dio"ide and carbon soot.3. %ral cancer is strongly associated ith cheing of tobacco. %ral cancer constitutes

2estern countries.*. Alcohol inta0e increases the ris0 of oral, pharyngeal, esophageal and liver cancers.

Diet high in total fat and cholesterol increases the ris0 of colon, breast and prostate

cancers.

Action o3 Che(ica' Carcinogens

1. Chemical carcinogens are ingested as procarcinogens. The en&ymes responsible for

the activation of procarcinogens are cytochrome 7$*< system .2. %n the other hand, direct carcinogens are the ones hich interact directly ith the

target molecules, e.g. methyl cholanthrene.

!HYSICA5 CARCINO,ENS

#$ray, gamma$ray and ?@$ray may cause)1. ormation of pyrimidine dimers,2. Apurinic sites ith conseuent brea0 in dna, and3. ormation of free radicals and supero"ides hich cause DA brea0, leading to somatic

mutations.*. !"posure of #$ray in fetal life ill increase the ris0 of leu0emia in childhood. (n

population studies, 1 rad per year ill increase the cancer incidence by *

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may contain either DA or A.2. @iral genes enter the cell and gets integration into the host DA. The drive for

multiplication by the virus genome overrules the regulatory chec0s of the cellular

mechanism. 5o, there is uncontrolled multiplication of the cells. This is called

transformation by oncogenic virus.+. H(an oncogenic "irses6

8irs Abbre"iati

on

Associate) h(an cancer

!pstein$'arr

virus

!'@ 'ur0itt;s lymphoma 9'/:E asopharyngeal

carcinoma 97C:

-uman

papilloma virus

-7@ ?terine cervical carcinoma

-epatitis '

virus

-'@ -epatoma

 ONCO,ENES6

1. The viral genes capable of causing cancer are originally 0non as oncogene. ormal cells

also contain DA seuences similar to viral oncogenes. These genes are called

protooncogenes.2. 7roto$oncogenes control normal cell groth and division.3. !"amples of proto$oncogenes)

a. Froth factors,b. Froth factor receptors,c. 5ignal transduction proteins,d. Transcription factors,e. Cell cycle regulators, andf. egulators of apoptosis.

*. The mutations in above proto oncogenes can give rise to oncogenes, an important step in

the causation of cancer.

. 4echanisms of converting the proto$oncogenes to oncogenes)a. Ra)iation an) che(ica' carcinogens act by producing a mutation in the coding

portion of the prto$oncogene converting into onccogenes.b. 8ira' insertionin to chro(oso(e)

i. >hen certain retroviruse 9genetic materia A: infect cells, a

complementary DA 9cDA: is made from their A by the en&yme reverse

transcriptase. The cDA so produced gets inserted into the host genome.

 This pro$viral DA ta0es over the control of the transcription of cellular

chromosomal DAii. 5ome DA viruses also get inserted in to the host chromosome and activate

the protooncogenes.c. Chro(oso(a' trans'ocation resulting in overe"pression of proto$oncogenes. !g.

'ur0itt;s lymphoma.d. ,ene a(&'i2cation) 5ome oncogenes result hen multiple copies of a proto$

oncogene are created. This occurs in certain drug administration li0e methotre"ate

and may cause resistance to cancer therapy.e. !oint (tation) (t refers to a change in a single base in the DA. The ras

protooncogene is an e"ample of activation by point mutation. The mutated ras

oncogene produces a protein 9FT7ase: hich diBers in structure by a single amino

acid. This alteration diminishes the activity of FT7ase, involved in the control of

cell groth.

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. Mechanis( o3 action o3 oncogenes)%ncogenes encode for oncoproteins. These proteins are involved in the transformation

and multiplication of cells.4. Onco&rotenes6

a. ,rowth 3actors6 ormally the cell proliferation is stimulated by groth factors.

%vere"pression andor structural alterations in groth factor receptors are

associated ith carcinogenesis. Transforming groth factor 9TF$d: is a proteinsynthesi&ed and reuired for the groth of epithelial cells. TF$a is produced in

high concentration in individuals suBering from psoriasis.b. ,rowth 3actor rece&tors) 5ome genes encoding groth factor receptors have

been identied to become oncogenes. !g.The overe"pression of gene erb$6,

encoding !C receptor is observed in lung cancer.a. ,T!9bin)ing &roteins) These are a group of signal transducing proteins.

Fuanosine triphosphate 9FT7:$binding proteins are found in about 3

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i. 5hort arm of chromosome 1 contain an oncosuppressor gene, called

p3. (t is so called because the gene encodes a &hosphoprotein ith

molecular eight /+,

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8. 5ince telomere shortening has been associated ith both malignant transformation

and aging, telomerase has become an attractive target for cancer chemotherapy and

drug development.

T7MOR MAR;ERS

1. What are t(or (ar:ers< !on Ma* #$$0#. Mention two t(or (ar:ers an) s&eci3* the )iagnostic a&&'ication M,R Ag

#$11+. T(or (ar:ers.

 Thay are also called as tumor inde" substances. They are factors released from the

tumor cells, hich could be detected in blood and therefore indicate the presence of

the tumor in the body.

C'inica''* I(&ortant T(or Mar:ers

1. A'&ha Feto&rotein =AF!>6

1. (t is fetal albumin and has similarities ith adult albumin. (t is increased in the

circulation of patients ith hepatocellular carcinoma, germ cell tumors,

teratocarcinoma of ovary and in pregnancy ith fetal malformations of neural tube .2. (n adult males and nonpregnant females, normal value is less than 1 ng/. A value of 

A7 above 3

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the tumor. (t is seen in blood as long as the tumor cells proliferate.3. The T7A blood test is sometimes used along ith other tumor mar0ers to help follo

patients being treated for lung, bladder, and many other cancers.

. !rostate S&eci2c Antigen =!SA>

1. (t is produced by secretory epithelium of prostate gland. (t is normally secreted into

seminal +uid, here it is necessary for the liuefaction of seminal coagulum. (t is a

glycoprotein. (t is a protease, and in serum it is seen comple"ed ith alpha$1$

antitrypsin.2. The 75A level, especially the comple"ed form, is increased in prostate cancers. 75A

has been found to be elevated in

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infections.b. (t is sometimes used along ith 4722 to test patients for the recurrence of

bladder cancer. This test is not often used. levels of CA$12 are also found in

appro"imately 2