CARCINOGENS Flashcards
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
