mutagenesis review deck

Question 1

5 types of endogenous mutations

Answer 1

oxidation of bases
alkylation of bases
hydrolysis of bases (includes deamination)
bulky adduct formation
mismatch of bases

Question 2

what is the result of C deamination?

Answer 2

C to U yields C –> T point mutation

Question 3

what is the result of A deamination?

Answer 3

A to HX yields A –> G point mutation

Question 4

what is the result of methyl C deamination?

Answer 4

methyl C to T, no repair possible

Question 5

what can trigger deamination? what can inhibit is?

Answer 5

nitrates in foods can trigger, vitamin C can inhibit

Question 6

5 types of exogenous mutations

Answer 6

ultraviolet radiation 
ionizing radiation
elevated temperature
lifestyle choices 
intercalators

Question 7

what are the consequences of UVB vs. UVA exposure?

Answer 7

UVB- forms pyridimine dimers, direct DNA damage

UVA- forms free radicals, indirect DNA damage

Question 8

by what mechanism does ionizing radiation cause mutations?

Answer 8

DNA strand breaks occur through the formation of OH- that reacts with C4’ and creates unstable intermediates

Question 9

what is the effect of elevated temperature on DNA?

Answer 9

increased rate of deprivation, single-stranded breaks in DNA

Question 10

how does smoking result in mutations?

Answer 10

creates benzopyrene, which is an intercalator

Question 11

what are intercalators?

Answer 11

substances that mimic normal purine and pyridimines, insert into DNA and disrupt replication and transcription

Question 12

what are the 3 intercalators discussed?

Answer 12

benzyprene (smoking), aflatoxin (mold), nitrogen mustard

Question 13

what is the effect of aflatoxin?

Answer 13

when activated, it conjugates to a base, forms a bulky adduct

Question 14

what is the effect of nitrogen mustard?

Answer 14

inter and intrastrand ligation

Question 15

in chemo, what do the “alkylating agents” do?

Answer 15

cross-link DNA and form adducts

Question 16

what are the alkylating agents?

Answer 16

cisplatin, carboplatin, cyclophosphamide

Question 17

in chemo, what do the “anti-metabolites” do?

Answer 17

inhibit DNA sythesis

Question 18

what are the anti-metabolites?

Answer 18

5-FU and methotrexate

Question 19

what is the MOA of doxorubicin and adriamycin?

Answer 19

inhibit topoisomerase II

Question 20

what is the MOA of taxol/paciltaxel?

Answer 20

bind b tubulin, stabilize MT assembly

Question 21

what is MOA of vincristine/vinblastine?

Answer 21

bind tubulin and MT assembly

Question 22

what is “transition”?

Answer 22

purine to purine; pyridimine to pyridimine

Question 23

what has “transversion”?

Answer 23

purine pyrimidine

Question 24

what is a clinical example of transversion

Answer 24

sickle cell anemia

GAG –> GTG