Carcinogens Flashcards
Define carcinogenesis
The process by which normal cells are transformed into cancer cells .
Its a multistep process
It results from accumulation of multiple mutations leading to damaged genes
Nonlethal genetic damage (mutation ) lies at the heart of carcinogenesis (caused by environmental and inherited )
Discuss the epidemiology of cancer
> Cancer is the common cause of death especially in the western countries
It accounts for 25% of all death
Major insight into the cause of cancer has been obtained by epidemiologic studies that relate to the environment, hereditary factors, and cultural influences
Discuss the causes of cancer
*Cancer is caused by damaged to genes . Commonly carcinogen exposure is involved
Discuss the various carcinogenic agents
Carcinogens agents come in various forms and may be seen in any situation eg chemicals, viruses,bacteria,fungi , parasites,ionising and non-ionizing radiation,hormones, and miscellaneous agents
How do occupational factors cause cancer?
Various occupations put individuals at risk of exposure to various carcinogens. This increase their likelihood of developing certain cancers
Example :
> Bladder carcinoma: beta-naphthylamine in people employed in rubber industries
> Radiation: Thyroid carcinoma, especially papillary thyroid carcinoma
*Chernobyl in Ukraine radiology
How does behavioral?
- Carcinoma of the cervix (Human papillomavirus ,sexually transmitted )
- Angiosarcoma of the liver ( Thorotrast ,a contrast medium in diagnostic radiology used between 1930-1950 )
- Lung carcinoma
* atmospheric pollutants
* smoking
How do chemical carcinogens cause cancer ?
when a cell is exposed to a chemical, the chemical can initiate damage to the cell. Sometimes the cells can either :
- be repaired
- apoptosis
- damage worsen causing the cell to mutate and proliferate
List the chemical carcinoma agents and the kinds of cancers they
Agent / Human cancer sites
>Asbestos /carcinoma of the lung, mesothelioma
List the chemical carcinoma agents and the kinds of cancers they
Agent / Human cancer sites
>Asbestos /carcinoma of the lung, mesothelioma
> Benzene / leukaemia ,Hodgkin lymphpma
> Vinyl chloride: Angiosarcoma of the liver
> Aflatoxin B : hepatocellular carcinoma
List the chemical carcinoma agents and the kinds of cancers they
Agent / Human cancer sites
>Asbestos /carcinoma of the lung, mesothelioma
> Benzene / leukaemia ,Hodgkin lymphpma
> Vinyl chloride: Angiosarcoma of the liver
> Aflatoxin B: hepatocellular carcinoma
How do viral carcinogens cause cancer?
> A large number of RNA and DNA viruses have proven to be oncogenic
Which RNA viruses are carcinogenic
- Hepatitis C virus > chronic inflammation > hepatocellular carcinoma
- Human T-cell leukaemia virus type 1(HTLV1) > adult T-cell > lyphoma /leukaemia
Which DNA viruses are carcinogenic
- Human papillomavirus
- Epstein -Barr virus
- Hepatitis B virus
- Human herpesvirus 8
Which DNA viruses are carcinogenic
- Human papillomavirus
- Epstein -Barr virus
- Hepatitis B virus ( also cause hepatocellular carcinoma )
- Human herpesvirus 8
How does Human papillomavirus carcinogens
> High risk eg 16 and 18
- Squamous cell carcinoma of the cervix, anogenital region, and oropharynx
- Integration of viral genome > malignant transformation
- HPV infection initiates an event and additional somatic mutations are needed to complete the carcinogenesis eg smoking, hormonal changes, dietary deficiency
> Low-risk types 6 and 11
causes genital warts
How do Epstein Barr virus carcinogens?
- Member of the herpes virus
- Infects epithelial cells of the oropharynx and b lymphocytes > immortalisation of b cells
*It is implicated in the pathogenesis of several human tumors eg burkitt lymphoma ,hodgkin lymphoma( cancer that originates from a type of WBC) and nasopharyngeal carcinoma
Oncogenic DNA viruses that are carcinogenic
- Hepatitis B virus
* Hepatocellular carcinoma
* Viral DNA is integrated into the host genome
* Causes chronic liver injury, regeneration, and cirrhosis
* Encodes HBx protein which disrupts normal growth control - HHV8
* Kaposi sarcoma
* Primary effusion lymphoma
How is fungi a carcinogen?
> Aflatoxin produced by aspergillus flavus is linked to high incidences of hepatocellular carcinoma
How are parasites carcinogens?
> Clonorchis Sinensis (Chinese liver fluke ) causes cholangiocarcinoma
> Schistosoma is strongly implicated in bladder squamous cell carcinoma in Egypt
How are bacteria carcinogens ?
- Helicobacter pylori
* Major cause of gastritis and peptic ulcer disease. It is implicated in gastric lymphoma (MALT lymphoma )and the treatment of the infection leads to regression of lymphoma. It is also associated with adenocarcinoma
List the 4 classes of normal regulatory genes that exist to prevent genetic damage?
- growth-promoting proto-oncogenes
- Growth-inhibiting tumor suppressor genes
- Genes which regulate programmed cell death
- Genes inc]volved in DNA repair
These all act at various stages of the cell cycle . For a tumor to start, there needs to be a mutation in one of these
Essential alteration for carcinogenesis to take place
7 marks
- Self sufficiency in growth signals - to promotes its own growth
- Insensitivity to growth inhibitory signals : to overcome growth inhibition
- Evasion of apoptosis : to avoid cell death
- Defects in DNA repair : so that repair of mutation does not occur
- Limitless replicative potential to avoid senescence
- Sustained angiogenesis
- Ability to invade and metastasize
T/F: A tumor is formed by clonal expansion of a single precursor cell that has incurred genetic damage
True
Discuss the multistep pathogenesis of cancer?
> It is a complex process
It is broadly made up of initiating event and promoting event(s)
The initiating event is understood to be an environmental attack causing genetic aberrations and (+- hereditary) and oncogenes are usually involved
Promotion is a series of increasing genetic aberrations > tumor suppressor genes usually involved
T/F: Only 2 mutations are needed in oncogenes to transform the cell but 1 mutation is needed in a tumor suppressor gene to transform the cell
False: Only 1 mutation is needed in oncogenes to transform the cell but 2 mutations are needed in a tumor suppressor gene to transform the cell
What are oncogenes and what is their role?
- Oncogenes promote cell growth in cancer cells
- Derived from normal cellular counterparts called proto-oncogenes
- Proto-oncogenes function by regulating cell proliferation and differentiation
- Products as growth factors and GF receptors, signal transducers, and nuclear factors
- Abnormalities include over and inappropriate expression or structural alterations
Give 6 examples of oncogenes?
k-ras: pancreatic and colonic adenocarcinomas H-ras: bladder carcinoma N-ras and BRAF: melanoma C-kit: gastrointestinal stromal tumor C-myc : Burkitt lymphoma
What are tumor suppressor genes
*They are categorised according to their mechanism of action .
> Caretaker gene : Maintain the intergrity of the genome by repairing dmage
Gate keepers : Inhibit the proliferation or promote the draeth of cells with damaged dna
List the tumor suppressor genes and their function
1.p53: Guardian of the genome because it has 3 critical functions
>initiates programs that result in cell arrest by preventing the transition of the cell cycle from G1 to S phase
>This allows time for cells to repair damaged DNA
> If the DNA damage cannot be repaired,p53 induces the cell to undergo apoptosis
- Rb1
* Originally described in childhood retinoblast and it regulates the G1-S checkpoint of the cell cycle
Genetic predisposition to cancer: If both my parents had cancer will I also suffer the same fate
Even though cancer is a genetic disease, not all cancers are hereditary because some mutations are acquired during a lifetime. Only 10% are hereditary
Genetic predisposition to cancer can be divided into 3 categories: list them
- Autosomal dominant inherited cancer syndrome
- Defective DNA repair syndrome
- Familial cancer
Discuss the AD inherited cancer syndrome
> Two-hit hypothesis postulated by Knudson
cancer syndrome is Usually due to a point mutation in a single allele of a tumor suppressor gene
2nd mutation occurs in somatic cells
> Retinoblastoma
*40% familial (AD)
(all somatic cells inherit one mutant gene and the second mutation occurs after birth )
*60% sporadic (Both mutations occur after birth )
*Two mutations of the RB locus lead to neoplastic transformation
Discuss the familial adenomatous polyposis
> It is an AD inherited cancer syndrome
AD mutation of the APC tumor suppressor gene
*Present with numerous colonic adenomas
*Develop carcinomas of the colon by age 50 in 100 % of the cases
Defective DNA repair syndrome
- Defects in DNA repair results in DNA instability
- Autosomal recessive
- Examples: hereditary nonpolyposis colon cancer and BRCA 1 and 2 >increaserisk of breast, ovarian, and prostate cancer as well as melanoma
Familial cancers
- Higher incidence of cancer in certain families without clearly defined pattern of transmission eg cancer of the colon, breast, ovary, and brain
- it occurs at younger age, tumors arising in two or more relatives of the index case and multiple or bilateral tumors
