Term
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Definition
| heritably altered autonomous growth tissue with abnormal regulation of gene expression |
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Term
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Definition
| neoplasm that does not undergo metastasis |
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Term
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Definition
| neoplasm that does undergo metastasis |
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Term
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Definition
| a secondary growth of cells from primary neoplasm |
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Term
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Definition
| in general, an agent that causes neoplasms * specifically, an agent whose administration to previously untreated animals leads to statistically significant increased incidence of neoplasms of one or more histogenetic typees compared with the incidence in untreated controls |
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Term
| When you're testing a chemical for its carcinogenicity, what do you look for? |
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Definition
| rare neoplasms, earlier induction of neoplasms, induction of more neoplasms than usually observed |
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Term
| What suffix is there when a 1st neoplasm is benign? |
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Definition
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Term
| What suffix is there when a 2nd neoplasm is mesenchymal in origin? Ectodermal? |
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Definition
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Term
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Definition
| chemical capable of only initiating cells |
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Term
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Definition
| chemical capable of causing the expansion of initiated cell clones |
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Term
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Definition
| chemical capable of converting an initiated cell or a cell in the stage of promotion to a potentially malignant cell |
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Term
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Definition
| chemical posessing the capability of inducing cancer from normal cells, usually posessing properties of initiating, promoting, and progressor agents |
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Term
| Name the 4 mechanisms of chemical carcinogenesis. |
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Definition
| metabolism of chemical carcinogens * generation of free radicals * mutagenesis * formation of DNA adducts |
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Term
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Definition
| chemicals that require metabolism for their carcinogenic effect |
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Term
| What is the reactivity of chemical carcinogens? |
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Definition
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Term
| What are free radicals and how do they induce cancer? |
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Definition
| chemical elements or compounds with an unpaired electron - react with DNA to produce structural changes in bases or they can react with procarcinogens to make them active carcinogens |
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Term
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Definition
| methyl or ethyl or other chemical groups that get added to DNA - they can be on the sugar, the phosphate, or the backbone |
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Term
| How can mutations be caused by DNA adducts result in? |
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Definition
| they can cause base mispairing or block DNA synthesis, |
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Term
| What are some common adducts or mutations in DNA that result from DNA reacting with a chemical? |
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Definition
| hydroxyl groups, methyl or ethyl groups, pyrimidine dimer formation, DS DNA strand breaks, DNA crosslinking via reactions between bases |
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Term
| What is the most common cause of pyrimidine dimer formation? |
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Definition
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Term
| What are the 2 damage response pathways when damage is discovered? |
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Definition
| repair or tolerance, which doesn't remove the damage, it just ignores it |
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Term
| What are the 2 repair mechanisms - when are they used? |
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Definition
| base excision repair - removal of a single altered base that has a low MW adduct, like a methyl group * nucleotide excision - removal of a base with a bulky group, like T-T dimers |
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Term
| Why can repair induce mutations? |
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Definition
| b/c polymerases can make mistakes as they repair - not being faithful to the template |
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Term
| Which repair process is more subject to mutations and why? |
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Definition
| nucleotide excision - there's a lot more bases removed than with base excision |
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Term
| What mutation is the hardest to repair without mistakes? |
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Definition
| double strand breaks - you have no template |
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Term
| What are the 5 steps in DNA repair? |
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Definition
| recognition of damage, unwinding the damaged strand, 3' and 5' incisions of the damaged strand, repair synthesis of the patch that's eliminated, ligation |
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Term
| Can DNA repair mechanisms be normal in a neoplastic cell? |
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Definition
| yes - it's just that in a rapidly dividing cell, repair mechs may not have time to work and the mutation stays |
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Term
| What are the 3 stages in cancer development? |
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Definition
| initiation, promotion, and progression |
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Term
| Discuss initiation. Is it reversible? What is required for fixation of a mutation? What processes are important? |
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Definition
| irreversible - this is where the genotype/phenotype of the cell is established * one or more rounds of cell division * metabolism, DNA repair, and cell proliferation are important |
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Term
| Can initiation be spontaneous? |
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Definition
| yes - but not all initiated cells survive over the life span of the organism due to apoptosis |
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Term
| What 3 genes are really important in initiation? |
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Definition
| proto-oncogenes, oncogenes, tumor suppressor genes |
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Term
| What are proto-oncogenes? |
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Definition
| genes that code for proteins that regulate growth factors, make signal transducers, and transcription factors |
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Term
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Definition
| proto-oncogenes that are mutated - usually results in uncontrolled growth |
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Term
| Which is the most important tumor suppressor gene? |
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Definition
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Term
| What are some characteristics of promotion - reversibility, exposure requirements, interaction of chemicals, and example? |
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Definition
| it is reversible (may be due to apoptosis)* cells must be continually exposed to the agent* promoting agents generally don't interact with DNA * saccharin |
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Term
| How exactly do promoters work? |
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Definition
| they usually alter or enhance certain signal transduction pathways or gene expression |
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Term
| What are the characteristics of progression? |
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Definition
| high growth rate, invasiveness, metastatic frequency, and hormonal responsiveness |
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Term
| What can progressor agents alter? |
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Definition
| the structure of DNA and/or chromosomes |
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Term
| What is the most common exogenous source of human cancer? |
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Definition
| cigarettes and other tobacco products |
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Term
| About how many carcinogens are there in cigarettes? |
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Definition
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Term
| Why does quitting smoking decrease the incidence of lung cancer? |
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Definition
| b/c promotion occupies the greatest time interval |
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Term
| Why is ethanol a carcinogen? |
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Definition
| it gets metabolized to acetaldehyde which is an incomplete carcinogen and can act as a co-carcinogen |
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Term
| What is aflatoxin? What is it associated with? |
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Definition
| a toxin made by some strains of mold like aspergillis - liver cancer in association with hepatitis B |
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Term
| What types of macromolecules in the diet are associated with cancer? |
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Definition
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Term
| What types of cancers can being overweight contribute to? |
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Definition
| prostate, colon, and breast |
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Term
| What increases the risk of ovarian and breast cancer? |
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Definition
| 1st child born after 40, increased risk of ovarian cancer if you never have children |
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Term
| What can UV radiation cause? |
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Definition
| skin cancer, cataracts, immune suppression |
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Term
| What stage of cancer are most methods of cancer prevention linked to? |
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Definition
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Term
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Definition
| a short term test for mutagenic potential |
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Term
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Definition
| Use mutant salmonella that can't make histidine - expose it to the chemical, plate on histidine-deficient media with liver microsomes - if it can grow there must have been a mutation - quantify the number of reverse mutations by counting the number of colonies that grow |
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Term
| Describe the dominant lethal test. |
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Definition
| expose male mice to a genotoxic agent, mate it with an untreated female and look for the number of pregnancies and the number of implants |
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Term
| Describe how transgenic mice are used to determine the mutagenic potential of a compound. |
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Definition
| a lot of them involve the lacI gene, which codes for B-galactosidase - you put part of the lac operon into the mouse and expose it to a carcinogen - wait for DNA replication, extract DNA from the tissue of interest and put it into a phage vector - infect E. coli with this vector and grow it on selective media - pick the colonies that grow and sequence the gene and look for mutations |
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Term
| How does the lac operon work? |
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Definition
| if lactose is not present, a repressor protein binds to the operator and no lac mRNA is made - when lactose is present, allolactose binds to the repressor, releasing it and allowing lac mRNA to be made |
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Term
| What is the gold standard for carcinogenesis? Describe it. |
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Definition
| chronic bioassays - 50 rats/sex, 2-3 dose and a control, unless historical controls are used - dose for 8-96 weeks, look for tumors |
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Term
| What is the big problem with chronic bioassays? |
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Definition
| you need a ton of animals |
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