Carcinogenesis Flashcards
General mechanisms of carcinogenesis
- Failure of DNA repair; 2. Failure of apopotosis; 3. failure of mitosis termination
Failure of DNA repair?
i. Epoxides bind to DNA; use excision repair
ii. Dose defines the poison–more epoxides on the DNA, the higher chance there is of the excision repair to make a mistake
iii. Xeroderma pigmentosum
1) Autosomal recessive trait; ER mechs don’t work
Failure of apoptosis
a. Mitosis vs apoptosis balance
b. Cancer cells have apoptosis signals turned off, and mitosis signal turned off
failure to terminate mitosis (cell prolif)
a. Nongenotoxic xenos cause cancers by inhibiting apoptosis ands timulating mitosis
3 stages of cancer development
initiation, promotion, progression
what is initiation?
a. Irreversible
b. Critical metabolic gene (ATP synthase) may be knocked out which prevents initiation from happening, but nothing cell can do about stopping initiation
c. Protoncogenes
i. Genes that get activated to protooncogenes, then activated to cancer genes, oncogenes
1) Oncogenes stimulate cell proliferations
d. Tumor suppressor genes inactivated
i. E.g. p53
what is promotion?
a. Can have initiation, but not end up with cancer–you need promotion (and progression)
b. Reversible
i. Certain xenos are promoters
c. E.g. lead is a promoter
i. Becomes involved in signalling pathways dealing with promotion
what are some promoters?
d. Hormones
e. Caloric intake
f. Ethanol
What is progression?
a. Benign growth to malignant growth
b. irreversible
c. Chromosomal changes
i. Chromosomal abberations
ii. Chromosomes linking together
iii. Become a different “cell”?
iv. Nubmer of chromos, morphology can change
what are complete carcinogens?
a. Are initiators, promotors, and progressors
E.g. tobacco (cigarettes)
what are the categories of carcinogens?
genotoxic; nongenotoxic; cocarcinogens; solid state carcinogens; metals
nongenotoxic carcinogens
DDTs, PCBs; endogenous mitogens; xenos that cause sustained cell injury
how do DDTs and PCBs cause cancer?
involved in stimulating mitosis and inhibiting apoptosis
what are the endogenous mitogens that can causecancer?
growth factors; estrogens and androgens
what xenos can cause cell injury?
chloroform; § Causes hepatotoxicity (liver necrosis)
§ The more cells that divide increases the probably of an incorrect mitotic event
what are cocarcinogens?
Not carcinogenic but increase the effect of a carcinogen (potentiation)
define neoplasia
new growth or autonomous growth of tissue
define neoplasm
the lesion resulting from neoplasm
define benign
lesions characterized by expansive growth, frequently exhibiting slow rates of proliferation that do not invade surrounding tissues
define malignant
lesions demonstrating invasive growth, capable of metastases to other tissues and organs
define metastases
secondary growths derived from a primary malignant neoplasm
define tumors
lesions characterized by swelling or increase in size which may or may not be neoplastic
define cancer
malignant neoplasm
define carcinogen
a physical or chemical agent that causes neoplasia
define genotoxic
carcinogens that interact with DNA resulting in mutation
define nongenotoxic
carcinogens that modify gene expression but do not damage DNA
what are examples of hormonal promoters?
i. Steroid hormones stimulate division of muscle cells
ii. Growth hormone
iii. Endocrine disrupting chemicals (EDCs)
1) Hormone mimics– present in plastics
how is caloric intake a promoter?
i. More energy intake, more energy and building blocks for cancer to use to proliferate
what kinds of cancer does ethanol promote
Promotes esophageal cancer, throat cancer
what are procarcinogens?
xenos that must first be activated to become carcinogenic (e.g. become epoxidated)
