3 carcinogenesis I Flashcards
what is chemical carcinogenesis?
induction of neoplasia (“new growth”) by chemicals
what is some terminology?
what does neoplasia and neoplasm mean?
-neoplasia=new growth or autonomous growth of tissue
-neoplasm=the lesion resulting from the neoplasia
what does benign and malignant mean?
-benign= lesions characterized by expansive growth, frequency exhibiting slow rates of proliferation that do not invade surrounding tissues
-malignant= lesions demonstrating invasive growth, capable of metastases to other tissues and organs
what does metastases, tumor and cancer mean?
-metastases=secondary growths derived from a primary malignant neoplasm
-tumor= lesions characterized by swelling or increase in size, may or may not be neoplastic
-cancer= malignant neoplasm
what does carcinogen, genotoxic, nongenotoxic mean?
-carcinogen= a physical or chemical agent that causes or induces neoplasia
-genotoxic= carcinogens that interact with DNA resulting in mutation
-nongenotoxic= carcinogens that modify gene expression but do not damage DNA
what is the weight of evidence?
evidence for cancer-causing chemicals comes from:
-i: human data (usually epidemiological)
-ii: laboratory animals (dose-response experiments)
what is the epidemiology of the causes of human cancer deaths?
“lifestyle carcinogenesis”-modifying factors (e.g. diet, nutrition, obesity, exercise, tobacco use)
what are the general mechanisms?
-cancer is a complex, multifactorial disease (>200 types of cancer)
-“malfunction” of various repair/protective processes:
1. failure of DNA repair
2. failure of apoptosis
3. failure to terminate cell proliferation
what are the three distinct stages of carcinogenesis?
initiation, promotion, and progression
neoplastic focal lesions in liver
what is step one of carcinogenesis?
-if cell with altered DNA undergo mitosis, the mutation is retained, and the cell is “initiated” (i.e. tumor cell that has altered genotype and phenotype); an irreversible event
-neoplasia often occurs when proto-oncogenes are converted (activated) to oncogenes (i.e. oncogenes created by mutation)
-also tumor suppressor genes; if they are inactivated through mutation, can lead to neoplasia
-e.g. p53 tumor suppressor gene is mutated in about half of all human cancers (“guardian of the genome”)
-recent evidence suggests that 26% of all breast cancers involved mutated p53
-thus, mutation of proto-oncogenes and tumor suppressor genes implicated in large number of human cancers
what are proto-oncogenes?
-proto-oncogenes normally code for proteins associated with cell proliferation; mutation of proto-oncogene (now an oncogene) results in permanent activation and/or overexpression of gene products; e.g. Ras
what is the graph that shows how tumor suppressor genes are “guardians of the genome”?
when irreparable DNA damage is detected by the cell and mdm2 falls off of p53
what is the summary of initiation?
-overall, accumulation of genetic damage in the form of mutant proto-oncogenes (encode activated proteins that increase mitosis) and mutant tumor suppressor genes (encode inactivated proteins that block mitosis) is the main driving force in changing normal cells with cell division “brakes” to malignant cells with “no brakes”
what is the summary of the steps of carcinogenesis?
