Mutagenesis

Question 1

what is the m/c form of base alkylation?

Answer 1

methylation

Question 2

what is typically true of the alkyl group that is added?

Answer 2

it is “reactive” like MNNG or mustard gas

Question 3

what are the possible outcomes of hydrolysis of bases? (3)

Answer 3

deamination
depurination
depyrimidation

Question 4

what bases can be deaminated?

Answer 4

C, methyl C, G and A

Question 5

what is the product/consequence of deaminated C?

Answer 5

C –> U, results in C –> T point mutation

Question 6

what is the product/consequence of deaminated A?

Answer 6

A –> HX, results in A –> G point mutation

Question 7

what is the product/consequence of deaminated methyl C?

Answer 7

methyl C –> T (cannot be distinguished from normal T, cannot be corrected)

Question 8

describe consequences of HNO2 exposure

Answer 8

HNO2 (nitrous acid) is a potent deaminator
produced from NO3 and NO2
Vit C can inhibit conversion

Question 9

what is the consequence of UVB exposure?

Answer 9

formation of pyrimidine dimers (T-T, C-T, C-C) that cause direct DNA damage

Question 10

what is the consequence of UVA exposure?

Answer 10

creation of free radicals that cause indirect DNA damage

Question 11

what is the consequence of gamma ray or Xray exposure?

Answer 11

causes single or double stranded DNA breaks through formation of OH- (hydroxyl free radical) that reacts with C4’ to yield unstable intermediates

Question 12

what is the consequence of elevated temperatures?

Answer 12

leads to increased rate of depurination and increased single strand breaks

Question 13

what are the consequences of tobacco smoking?

Answer 13

smoking leads to the creation of benzopyrene

Question 14

what is benzopyrene?

Answer 14

intercalator- has planar ring structure that allows it to mimic normal purine and pyrimidines and will disrupt replication and transcription (can induce frame shifts, mutations)

Question 15

what are the alkylating chemo drugs?

Answer 15

cyclophosphamide, cisplatin and carboplatin

Question 16

how do the alkylating chemo drugs work?

Answer 16

cross-link DNA and form DNA adducts

Question 17

what are the anti-metabolite chemo drugs?

Answer 17

methotrexate and 5-FU

Question 18

what is the MOA of methotrexate?

Answer 18

mimics tetrahydrofolate, inhibits DNA synthesis

Question 19

what is the MOA of 5-FU?

Answer 19

completes with uracil

inhibits DNA synthesis

Question 20

what is the MOA of doxorubicin and andriamycin?

Answer 20

inhibit topoisomerase II

Question 21

what is the MOA of taxol/paciltaxel, vincristine/vinblastine?

Answer 21

binds b-tubulin and stabilizes MT assembly

Question 22

what are other intercalators aside from benzopyrene?

Answer 22

actinomycin D
aflatoxin
echinomycin

Question 23

what are the 2 enzymes that the liver uses to detoxify aflatoxin?

Answer 23

epoxide hydrase

gluthathione 5-transferase

Question 24

how does XRT work?

Answer 24

induces apoptosis through double stranded DNA breaks and reactive oxygen species

Question 25

what is a “transition”

Answer 25

pyrimidine to pyrimidine or purine to purine

Question 26

what is a “transversion”

Answer 26

pyrimidine purine

Question 27

what is a clinical example of transversion

Answer 27

sickle cell anemia

GAG –> GTG leads to Glu –> Val

Question 28

what is a clinical example of deletion

Answer 28

cystic fibrosis

Question 29

what is a clinical example of insertion

Answer 29

fragile X- amplification and insertion of (CGG) x 200 on the X chromosome

Question 30

what are the 5 types of endogenous DNA mutations?

Answer 30

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