Development and progression of malignancies is a multi-step process involving number of genetic changes over a period of time as a result of continuous exposure to chemical physical viral or any other carcinogenic agent.
Risk factors for a cancer
The possible causative agents of carcinogenesis
Cancers associated with chronic diseases
What happens when exposed
Radiation causes its effect by transferring energy to the substance through which it passes
Result may be:
Change in the energy state of the electrons or charged molecules.
X rays , , and rays
These agents injure the cells through which it pass by dislodging ions from water and other molecules– Formation of free radicals.
React with DNA nucleic acids, proteins,and other molecules.
DNA damages may be;
Point mutation (Changes in single bases) Breaks in the DNA double strand (wrong reunion)
Lethal doses - Immediate cell death
Sub lethal doses - Permanent damage in DNA. Malignant transformation.
Effect of the radiation on different tissues depends on the
Nature of the tissues (Bone)
Type of radiation (Determined the depth of penetration)
Evidence to show effects of ionized radiation
Nuclear weapons testing; Radio strontium
Hiroshima and Nagasaki (1945) - leukaemias & other cancers
Dial painters (Osteosarcomas).
Farmers with fair skin who have no melanin protection. (Solar keratosis)
Squamous cell carcinomas
Basel cell carcinomas
Mechanism; Dimmer formation between bases E.g.:Thymidine bases in the DNA.
(Dimer causes mutation in DNA replication)
Lack of enzyme involved in the repair mechanism of damaged DNA.
Relationship between neoplasia and hormones is complex.
Animal experiments to show hormonal involvement in carcinogenesis:
High cancer strains oestregen Breast cancers Low cancer strains oestregen Hyperplasia
Mice or rats.
Two ovaries were removed and one implanted in the spleen to stop the feed back inhibition of pituitary. (result is occasional ovarian tumours)
Mice or rats
Low I, diet and thiouracil
Reduce thyroxin formation (no feed back effect)
Result is thyroid hyperplasia/ademoma/carcinomas
However evidence of hormonal involvement in human tumours are rare. But association of hormones in tumours in man have been shown
Granular cell OESTROGEN tumour of the ovary Endometrial Endometrial hyperplasia Carcinoma
Artificial sex Oestrogen Enlargement of change Breast Carcinoma Hyperplasia
Hormone dependency ;
Even though the role of hormones in the aetiology of tumours is not clear, it is clear that hormones are important in maintaining of some tumours. Administration Progress the growth Deprival Regress the tumour eg; prostate
30% Breast tumours, are hormone dependent
Later hormonal dependent Independent.
Hereditary predisposition ;
Cancer of the breast
Polyposis coli: Autosomal dominant
Virus and cancer
Ellerman and Band (1908)
Chicken Cell free extract Erythroid leukaemia
Chicken Cell free extract Sarcoma of sarcoma
Foster mothers from cancer free strains New bone mice with cancer susceptible strains
New bone mice from cancer free strains
Foster mothers from cancer strains
Both RNA and DNA viruses have been shown to be capable of causing cancers in various vertebrate species including man.
Integrate there genetic material into the DNA of the host cell.
98% of the tumour cells show EBV genom
High antibody levels in the serum.
Human papilloma virus.
Type 5.6,11 papillomas
Type 16 & 18 involved in cervical carcinomas.
Hepatitis B: Hepatocellular carcinoma.
Epidemiological evidence shows that there is a large number of chemicals with carcinogenic properties
Eg Industrial cancers (Occupational cancers);
Result of prolong exposure to chemical carcinogens.
Scrotal cancers - Chimney sweepers (Percival Pott in 1775)
Skin cancers - Tar workers
Bladder cancers - Aniline die workers (1895)
Liver angiosarcomas - PVC factory workers
Lung cancers - Asbestos workers
Experimental evidence for chemical carcinogens
1917 (Yamagiwa and Itchikawa)
Coal tar application in rabbit skins Polycyclic hydrocarbons ; Dibenzanthracene Methyl cholanthrene
It has been shown that most of the Poly cyclic hydrocarbons, Aromatic amines Nitrosamines, aflatoxins are carcinogenic.
mineral oils/fuels, atmosphere of industrialized cities