in vitro

Question 1

three R’s

Answer 1

replacement - alternatives developed by pharmaceutical industry (some replacement methods have been accepted by regulators)
reduction - of animal numbers in research, toxicological studies
refinement - methods that eliminate or minimize pain /distress on animal

Question 2

what is the goal of pharmaceutical industry?

Answer 2

to broaden number of validated and accepted alternative methods

Question 3

genotoxicity

Answer 3

any deleterious change in genetic material regardless of mechanism where change is induced

Question 4

genetic endpoint

Answer 4

precise type or class of genetic change investigated

Question 5

mutagen

Answer 5

an agent that makes dna damage and other permanent genetic alteration with changes in one or more dna base pairs

Question 6

clastagen

Answer 6

an agent that makes structural or numerical changes in chromosomes usually detectable by light microscopy

Question 7

unschedules dna synthesis

Answer 7

damage to dna requires cell to make new dna to compensate for loss or damage

Question 8

DEREK

Answer 8

knowledge based expert system for qualitative prediction of toxicity, mainly for genotoxicity/carcinogenicity
DEREK not a database system but a rule base system. each rules describes relationship between a structural feature and its associated toxicity

Question 9

what does DEREK stand for?

Answer 9

Deductive Estimation of Risk from Existing Knowledge

Question 10

ames test

Answer 10

screen for induction of point mutations

Question 11

micronucleus test

Answer 11

screens for clastogenic/aneugenic activity in mouse lymphoma cells
quick results
also detects apoptotic/necrotic activity
performed in vitro or in vivo

Question 12

chromosomal aberration test with human lymphocytes (HCA)

Answer 12

cytogenic test for detection of chromosomal damage in human lymphocytes, +/- liver homogenate (S9)

in vitro assay that looks at chromosomal damageusing human lympcyte by sampling blood with +/- S9 then looking at the cells in a slide undermicroscope to see anuegenic potential and clastogenic potential

Question 13

mouse lymphoma cell mutation test (ML/Tk)

Answer 13

test for induction chromosomal aberration and gene mutations in mouse lymphoma cells, +/- liver homogenate (S9)
minimal drug required and quick results

Question 14

Genotoxicity

Answer 14

seen only as predictor of carcinogenicity

Question 15

why are there diff results in vitro and in vivo?

Answer 15

drug is metabolized differently
genotoxic metabolites not generated in vivo
genotoxic product doesnt reach target cell in vivo
genotoxic products are metabolically inactivated
different blood levels

Question 16

additional testes are

Answer 16

phospholipids and phototoxicity

Question 17

photoxicity

Answer 17

light induced non immnologic skin response to a photoreactive drug or chemical

Question 18

chemical photosensitivity

Answer 18

adverse cutaneous reaction from drugs at same time that a person is exposed to uv or visible radiation

Question 19

photoallergy

Answer 19

acquired altered reactivity of skn that is dependen on antigen-antibody or cell mediated hypersensitivity

Question 20

UV-B

Answer 20

cause of burning tanning aging and carcinogenity

Question 21

UV-A

Answer 21

erthrogenic and melanogenic; associated with photosentization

Question 22

3T3 fibroblast neutral red uptake assay

Answer 22

Exposure to drug
cells are preincubated with various drugs in buffer
cells are washed and incubated overnight in basal culture medium

Readout parameter
measurement of neutral red uptake into cells.