Mutagen, Carcinogen, And Teratogen

Front 1

What are mutagens?

Back 1

Chemical agents that cause heritable changes in genes

Front 2

What are carcinogen?

Back 2

Chemical agents that cause cancer?

Front 3

What are teratogens?

Back 3

Chemical agents that cause birth defect?

Front 4

What types of mutations associated with Therapeutic drugs?

Back 4

Point Mutations

Alkylating

Frameshift mutations

Doxorubicin

Chromosome rearrangements

Alkylating, cisplatin

Aneuploidy - drugs that affect microtubulesVinca alkaloids, taxane

Front 5

What is doxorubicin?

Back 5

Intercalating agent stacks on top of nucleotides. When DNA polymerase go over, it may skip over that area( point mutation) or insert a base where it should be

Front 6

What causes the breakage associated with DNA crosslinking agents?

Back 6

The breakage is due to DNA REPAIR.

Front 7

What is the evidence to conclude that breakage is associatd with dna repair?

Back 7

Bacteria that have mutations in mismatch repair genes are less sensitive than wild type bacteria to the effects of DNA crosslinking agents

Front 8

What is aneuploidy caused by?

Back 8

Cfhromosome nondisjunction when theres a defectine mitotic spindle checkpoint

# some has more chromosomes than other uneven

Front 9

What are the methods for detectding mutagenic properties of drugs?

Back 9

Ames test

Drosophilia recessive lethal test

mouse domnant lethal test

Micronucleus test

Chromosome painting

Front 10

What is the ames test?

Back 10

You have a strain that is his - which means it can create it and add extract it liver. Known for metabolism.

Then add chemical to it to see if theres any growth because the growth means there was a mutation to revert it

You have to check if metabolziing the chemical by liver enzyme can create mutagens or the drug itself is a mutagen in its regular form

Front 11

What is the recessive lethal test?

Back 11

First the parent class will be a female wthat is heterozygous for bar and recessie lethal mutaion and a wild type male exposed to a suspected mutagen

Therefore you hate mthe f1 bar eye females with normal males.

Then you count the males, if no males were shown, mutagen wouldve been prodiced beacused it would be inherit.

HOwever if its not, there should be half alive half death, the half dead should be bar eye(from mother)

Front 12

What is the dominant lethal test?

Back 12

Mutagenize males and mate with normal female

Sacrifice pregnant females just before the bith of the f1 generation

Examine the ratio, dead embryo means that it has domiannt mutation..

Front 13

What is the micronucleus test?

Back 13

Exposed animals with mutagen

Treat culture lympochotes with cytochalisin b( stop mitosis)

Stain cells with dna binding dye and look for bi nucleate cells with a micronucleus ( look fro mono/bi nucleate want to examine the ones are undergoing division

The presence of micornucleus shows that there are chromosomes that are not properly seprated therefore create their own circle

You do fisih to distignuish beetween micronucleu with a whole chromosome and accentric chromosome. Naturally whole chromosome means that it was because of mutagens however accentric chromosome is due to not having a centromere for dividng

Front 14

What is chromosome paintaining?

Back 14

Painting the chromosome to see any defectes

Process: Add colchine, make them arrest in mitosis and suspend the cell in acetic /ethanol to rupture it

Specifically binding unique chromosome dyes that binds to satellite dna

Front 15

What are the mutagens that suspected to being carcinogens?

Back 15

Drugs: alkylating agents, alkaloids, taxanes

Foods: Saccharin

Front 16

What are the guidelines for testing for potential carcinogens?

Back 16

1. Relatively large number of animals

2. Animals must be maintained on the drug major proportion of their life

3. Two or more species

4. Tested in pregnant females and test offpsring for their lifetime

5. Route of administration in the animal should be the same as for humans

6. Dosage rage must be higher than for propose human(10-100x ) the human exposure so you can extrapolate

Front 17

What is the relationship between Initiation and Promotion?

Back 17

You need both of them to occur a tumor incidence with initatior before the promoter

Front 18

What are the features of initation and promotion?

Back 18

Iniation: mostly mutagens where the mutations occur , heritable ganes

Promoters: activate cell proliferiation where now youre making cells with this mtuagens

Initation must comes first . Then rpometers make carcinogen mutation

Promoter may be added long after application of initatior

Front 19

Back 19

Initatior; Shows a linear response where as you increase the levels of them tuagen you get noticeable biological affects

Promoters: Sigmoidal curve where iitially the dosage wont show any biological affect but it s biological effect increase a certain dosage and levesl off

Therefore, you can possible use a promotersas long as it doesnt hit the thershold, not for mtuagen though

Front 20

What is nitrosodiethylamine

Back 20

A possible carcinogen however, by extrapolating the adta, i shows that it shows a sigmoidal curve

Front 21

How does metabolism affect carcinogencity?

Back 21

It can either increase or decrease it.

In terms of benzoprene, it is not a carcinogen until p450 metabolize it it to a carcingen

Front 22

What is teratogenesis?

Back 22

Birth defect in babies/embryo

1. Time of exposure is critical: 2-10 weeks for most teratogens in humans( period of major organogensis)

2. Alteration not heritable doesnt dea with genes

3. Specific malformation depends ontime of exposure during fetal development

4. significant species difference

Front 23

What are known human teratogens?

Back 23

Thalidomide

Warfarin

Corticosteroids

Diethylstilbestrol

Phenytoin/antiepilpetics

Cytoti dna damaging anticancer drugs

Retinoids

ACE inhibitor( teratogenic all preg) - renal pathway

Ethanol

Front 24

What is Thaliomide?

Back 24

Produced as a safe drug for pregnant woman to deal with morning sickness.

Has safe R and toxic S

Affects include phocomelia and major organ dects

Was not approved by fda but yet still on the market

Front 25

What is the approved use of Thaliomides?

Back 25

Treat : Erythema nodosum leprosum

Myeloma

Both patients and physcian must be enroeld in STEP before drug can be used

Work as an antiogenesis inhibitor

bloodcot/neuropathy

Front 26

What is Diethystilbesterol?

Back 26

DES

Used from 1940-1970 to prevent miscarriage

Female offspring who used DES showed vaginal neoplasia at puberty and increased risk of vaginal /cervical cancer