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PA 2307- Mod 8 > CARCINOGENS > Flashcards

Flashcards in CARCINOGENS Deck (20)
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how much of deaths does cancer cause

25% NA adults will be diagnosed w cancer
leading cause of death in <15


what is genotoxicity vs cytotoxicity

Genotoxicity- toxicity of genetic material via electrophillic attack

cytotoxicity- cellular toxicity notably lipid peroxidation


is there a totaly safe dose for carcinogens

no (but may be a threshold dose just hard to experiment for it)


What is pro proximate and ultimate carcinogens and thru what system is it biotransformed

Procarcinogen- original molecule
proximate- intermediate
ultimate- actual carcinogenic compound

usually p450 but can also use phase II in rare instances


How is benzoapyrene detoxified

glutathione is used to detolxify it


What are the 3 major steps to cancer development

matabolic activation- biotransformation of substances
Initiation- beginnings of heritable changes
promotion/progression- propagation of genetically altered cells


what is the indirect steps of carcigogen progression

-precarcinogen may be detoxified to a non carcinogen (conjugation)
-electrophillic ultimate carcinogen produced
- if not further detoxified it will covalently interact w tissue genetic tissue resulting in heritable genetic changes
-if not repaired it can lead to activation of oncogenes and inactivatoon of tumor suppressor genes


How does the direct steps of carcinogen progression work

does not require activation through biotransformation and metabolism
-alkylating agent will covalently bind an alkyl group on DNA/RNA creating heritable change


What is characteristics about the intiator in cancer progression

initiator must be given before the promotor
-repeated doses of initiator may cause tumors in the absence of prompt and produces irreversible change


Is exposure to the promotor reversible

exposure to the promotor is usually repeated and the action seems reversible


what bac is used for the ames test

salmonella that can’t synthesize histadine


Ames test- what is a direct acting mutagen and mutagen requiring metabolic activation

direct acting- irrespective of microsomal prep the chem will be a mutagen

metabolic activation- needs microsomal S9 prep (that contains p450 activity) for mutagen activity


What do alkaylating agents do

bind covelently to DNA
(act against tumor but also to normal cells)


What is the dosing regimne like in anti neoplastic drugs

high acute dose--> alow recovery from toxicity in other parts of the body--> administer next high dose


What is the sig of a 1-g tumor mass

smallest tumor burden that is physically detectable
-clinical symptoms usually first appear at this stage


What is curative chemotherapy (solid tumors)

tumor burden initatially reduced by sugery/radiation
-tx then continued till cancer disapeard


What is curative chemotherapy (disseminated tumors)

-combo drug therapy reduces chance of drug resistence


What is a clonogenic cell

has pot for unlimited replication
-effectiveness of chemo will depend on its ability to eliminate all clonogenic cells


what type of kinetics does antineoplastic driugs follow

first order kinetics


What is the best dosing schedal

high dose intermiuttent scheduals more effective than low dose daily management