Tox Ch. 6 - 7

Front 1

phys/chem agents that cause DNA damage are called

Back 1

genotoxic

Front 2

a hallmark of cancer is ____ instability at the ___ and ___ level

Back 2

genetic; molecular (mutagenesis- point mutations, base subst, small changes) and chromosomal (aneuploidy, clastogenesis - break, rearrange, loss of fragments of chromos)

Front 3

DNA repair processes

Back 3

proofreading during replication, mismatch repair, direct damage reversal

Back 4

base excision, neucleotide excision, postreplication repair

Front 5

Not every mutation leads to initiation! Mutation in which genes does?

Back 5

oncogenes (point mutation, activation, translation); tumor suppressor genes (deletion, translocation)

Front 6

what is a non mutagenic way of getting cancer?

Back 6

if cell expression is amplified by modification of proto-oncogene, more of that gene product can lead to cancer w/o mutation

Front 7

what is BRCA?

Back 7

breast-cancer tumor suppressor gene; pop risk and prev are low but abs risk and strength of assoc very high; necessary and sufficient for D+ causation

Front 8

dif b/w single genes and susceptibility genes

Back 8

necessary and sufficient to cause D+, low pop prev but high abs risk and strength of assoc, interaction w/ enviro is 2nd degree and variable, (opp is true for susceptibility genes)

Front 9

describe relationship b/w mutagenicity and carcinogenicity

Back 9

almost all mutagens are carcinogenic but not all carcinogens are mutagenic

Front 10

promoters can target site of tumors --> organ specificity

Front 11

what is an epigenetic change?

Back 11

any change in gene expression that does not effect DNA sequence (often methylation, acetylation), can be heritable, can result in carcigenicity --> change in histones via methylation, acetylation det how densely chromatin packs and how accesible it is to transcrip factors

Front 12

enviro factors may contribute to ___ % of all cancers

Back 12

75%

Front 13

exs of acute tox testing

Back 13

LD50 (being phased out b/c inhumane, req lots of animals, may not provide accurate way of assessing human risk, can use up-down and limit test which use fewer animals to det characterize but not asses risk (b/c not stat sig)

Front 14

explain repeat-dose / subchronic tox tests

Back 14

repeat dosage every 60 or 90 days to see effects of bioaccumulation on non-lethal D, provides info on target organ toxicity, establishes dose regimens for chronic studies, give info to estimate MTD (maximum tolerated dose) = no sig impairment of growth / observable toxicity, can be used to estimate NOAEL, LOAEL, BMD but w/ added UF b/c chronic is best

Front 15

chronic tox testing

Back 15

to det chronic effects, carcinogenicity, over better part of animal's lifestyle, pref method to establish NOAEL, LOAEL, BMD

Front 16

in vitro tox tests

Back 16

cellular tox (has basically replaced animal studies) and genotoxicity: (structure/activity - possibility of becoming mutagen by ID reactive sites or possible reactive sites post-biotransformation, mutagenecity (AMES - add P450s to biotransform), chromosomal damage, DNA damage)

Front 17

advantages of in vitro tox testing

Back 17

fewer animals, cheaper, potential for use in high-throughput screening assays, uniform bio systems (cell lines), more control over exp - enviro cond, chem [ ]

Front 18

disadvantages of in vitro tox testing

Back 18

loss of organ struc and cell-to-cell interac, static regarding nutrient influx, metabolite accum, short-term, loss of diff tissue, cell-specific activity (ability to biotransform!), regulatory acceptance, harmonization

Front 19

issues w/ establishing a D-R relationship

Back 19

association vs causation, expo, not dose, response relationship, plausible bio mechanims

Front 20

2 types of trad D-R relationships

Back 20

continuous/graded, quantal (yes/no) - assume normal distr and plot curve of yes/no at dif doses

Front 21

what's responsible for steep slope at beginning of D-R curve?

Back 21

saturation of body's defense mechs, induction, or some other biotransformation of enzymes

Front 22

why is quantal curve a full parabola? What does either end mean in terms of describing pop?

Back 22

left = susceptible pop, right tail = resistant pop (normal distr in terms of pop)

Front 23

pop response of D or not depends on ___ and ___

Back 23

background expo and vulnerability

Front 24

2 types of non-trad D-R curves

Back 24

U-shaped (essential nutrients), hermetic (hormones)

Front 25

what is the reference dose and how do you calc it?

Back 25

estimated daily dose that is likely to have no appreciable affect over lifetime of expo: NOAEL or LOAEL/Ufs

Front 26

Ufs

Back 26

animal--> human, use of less than chronic data, inter-individ, use of LOAEL instead of NOAEL

Front 27

dist b/w safe human dose / Rfd and actual human exposure is called

Back 27

margin of expo - should be as large as possible (bigger than expo by factor of 100 or 1000)

Front 28

why is calc a point of departure via benchmark dose (and then applying UF to find MOE) better than using RfD and NOAEL or LOAEL?

Back 28

uses entire D-R curve b/c plot 95% CI (upper line = upper response, lower dose limits) instead of just NOAEL or LOAEL

Front 29

how extrapolate from D-R for carcinogen?

Back 29

straight line from last pt to graph's origin --> non-threshold

Front 30

VSD is what?

Back 30

virtually safe dose - purpose of the cancer model (chronic); at very low doses, below experimental levels

Front 31

what is the main test for carcinogenicity?

Back 31

Ames