Tox Ch. 4 - 5

Front 1

define biomonitoring

Back 1

using biomarkers to measure changes in body burden of chem compounds, elements, their metabolites

Front 2

define molec epi

Back 2

incorporation of biomarkers into analytic, epi resesarch

Front 3

what are some probs in det causation factors of D in pub health?

Back 3

multi-exposures, variation in suscept/response, long latency pds of D, low levels - chronic

Front 4

what are some dif types of exposures?

Back 4

concentrated, cyclic, intermittent, random, continuous

Front 5

benefit of biomarkers?

Back 5

incorporate multiple expo of dif types, mult routes of entry

Front 6

to measure biologically effective dose, measure __

Back 6

covalently, irreversibly bound active form of xenobiotic w/ molec target (adduct) - when measuring adduct you are always measuring bio effective dose

Front 7

why is it easier to measure DNA adducts (like in urine) than proteins?

Back 7

DNA has 4 target bases so pretty easy to ID carcinogen, proteins have tons of AA and we're not as sure abt the target

Front 8

why measure hemoglobin and albumin adducts if you're studying a carcinogen whose target is DNA?

Back 8

even tho adduct may be unrelated to D+, still gives you idea of level of bio effective dose b/c DNA may be too hard to meausre

Front 9

markers of early biological effect

Back 9

mutated oncogenes, suppression of tumor suppressor genes (p53 gene), gene rearrangements + enzymatic activity(early bio effect b/c can ID mutations and potential cancer before symptoms develop)

Front 10

2 jobs/roles of both oncogenes and tumor suppresor genes

Back 10

gatekeepers (control when) and caretakers (control integrity of DNA) in cell reproduc

Front 11

one lab technique used to look for mutated DNA

Back 11

mass spec - dif bases have dif molec weights

Front 12

markers of altered struc/func

Back 12

serum markers, urine markers (presence of glucose, proteins, etc)

Front 13

factors affecting choice in biomarker

Back 13

practical: inexpensive, easy/quick, high throughout; analytic: precise, valid, accurate; biological: dynamic (can modulate effect and see add/diminishing biomarker), surrogacy: amt of chemopreventive agent explained by modulation of that biological ageant

Front 14

define pharmacogenetics

Back 14

looking at effect of drug / side effects on individ by looking at effect on specific genes / SNPs --> to develop more personalized med

Front 15

exs of genetic mutations resulting in inc susceptibility to D

Back 15

heterozygous for sickle cell (mutation in hemoglobin), mutation in DNA --> dec repair capability = inc sensitivity to carcinogens (failure to repair UV damage to DNA, failure in replication or repair of double strand DNA breaks)

Front 16

what happens to DNA repair capacity as you age?

Back 16

decreases in normal pop

Front 17

how do you assess DNA repair capacity in an individual?

Back 17

plasmid-host cell reactivating assay

Front 18

what is PBPK testing?

Back 18

use of a mathematical model to describe absorbtion, distribution, biotransformation of a chem to reduce uncertanities in det est dose of expo (uses physiology and data from animal studies), has been very effective for many chem, not every effective for toxicodynamics

Front 19

why is PBPK testing so powerful?

Back 19

overcomes prob of dealing w/ saturation of biotransformation at high doses

Front 20

Define dif levels of PH prevention

Back 20

primary (prevent initial dev of D+: red exposure, vaccination); 2nd (red effect/severity of D thru screening, early detec), 3rd (red impact of D: rehab)

Front 21

primary prevention strategies in tox

Back 21

reduce expo thru reg agencies (EPA, NIOSH), reduc body burden (absorb paraquat via diatomacious earth, inc urinary excretion of a chem)

Front 22

secondary prevention strategies in tox

Back 22

reduction of bio effective dose: induce phase II enzymes like glutathione - cellular defense, mucomist)

Front 23

tertiary prevention strategies in tox

Front 24

mycotoxin; stressors

Back 24

natural toxicant from fungus (aflatoxin); high temp, low water (droughts), insect stress

Front 25

dif b/w toxin and toxicant

Back 25

toxin = natural, toxicant = man made

Front 26

greatest regions of concern for aflatoxin in U.S

Back 26

corn and peanuts in SE, cotton in SW

Front 27

acute aflatoxicosis in humans characterized by

Back 27

vomiting, ab pain, pulm edema, fatty infiltration + necrosis of liver; also a carcinogen, mutagen

Front 28

describe how aflatoxin works to create toxicity

Back 28

turned into electrophile by P450 in liver and can be turned into stable, water sol, excretable compound via Phase II enzyme or can target guanine in DNA and mutate P53 gene; unstable aflatoxin-DNA adduct can be measured in urine

Front 29

describe carcinogenicity of aflatoxin

Back 29

has a synergistic effect w/ hep b in causing HCC (hepatocellular carcinoma - a type of liver cancer), high case fatality

Front 30

why were residents of Qidong under so much threat from aflatoxin?

Back 30

diet consisted of all vulnerable foods, coastal (hotter, humid - good conditions for D), prep - on ground, storage - thru winter (aflatoxin grows on post-harvest)

Front 31

strategies for primary prevention of HCC in Qidong

Back 31

vaccination against hep b, aflatoxin harvest tech: improve food storage, biocontrol (insecticides), changes in dietary staples

Front 32

secondary prevention strategies for HCC in Qidong

Back 32

red severity of D: chemopreventive interventions (retard, block, reverse process of carcinogenesis before malignancy, using natural or man-made methods): chlorophyllin binds to aflatoxin and is excreted; sharply reduces # of aflatoxin-DNA adducts -> brocolli sprouts (look for sulphoraphane biomarker in urine - high level = good)

Front 33

What is a plasmid-host cell reactivation assay?

Back 33

technique used to measure the repair capacity of cell of a particular DNA alteration. The host cell is transfected with a damaged plasmid containing a reporter gene, usually luciferase, which has been deactivated due to the damage. The ability of the cell to repair the damage in the plasmid after it is introduced to the cell allows the reporter gene to be reactivated leading it to produce its reporting product.

Front 34

what is a transcription factor?

Back 34

a protein that binds to specific regions in DNA (usu in promoter region) and controls transcription

Front 35

How does p53 function?

Back 35

a tumor suppressor gene that is activated by oxidative stress, DNA damage, etc to undergo conformational change which allows it to sit on DNA in promotor regions of DNA of other transcription factors / inhibitors that stop/pause cell growth to give time for DNA repairs or apoptosis; when a chem, virus, or radiation mutates it, its ability to do this may be lost