13: Genotoxicity and Carcinogenicity of Drugs

Question 1

new or autonomous growth of tissue (neoplasia) resulting in formation of a lesion named neoplasm

Answer 1

carcinogenesis

Question 2

abnormal tissue growth

Answer 2

carcinogenesis

Question 3

malignant neoplasm, disease characterized by mutation, modified gene expression, cell proliferation, and aberrant cell growth

Answer 3

cancer

Question 4

what is carcinogens

Answer 4

physical or chemical agent that causes of induces neoplasma

Question 5

what is the process of forming a neoplasm called

Answer 5

carcinogenesis

Question 6

what is a tumor

Answer 6

lesions characterized by swelling or increase in size, may or may not be neoplastic

Question 7

agent/ process that interacts with cellular DNA, resulting in alteration of DNA structure

Answer 7

genotoxic

Question 8

3 cellular basis of cancer

Answer 8

Uncontrolled and inappropriate division of cells
Genetic damage to critical genes that regulate cell growth
Exposure to chemical carcinogens considered important

Question 9

chemical carcinogenicity is determined by

Answer 9

epidemiological studies- relationship between cancer sus agent and human population
animal studies- at least 2 species with varying dose and time

Question 10

which stage is reversible
1. initiation
2. promotion
3. progression
4. metastasis

Answer 10

2

Question 11

which carcinogenesis stages are irreversible

Answer 11

initiation
progression

Question 12

in proliferation, what is reduced?

Answer 12

apoptosis

Question 13

what point of the carcinogeneis process do drugs tend to target

Answer 13

promotion

Question 14

the initiation stage of cancer is _______ and ____

Answer 14

rapid and ireversible

Question 15

3 steps of initiation include

Answer 15

DNA modification by initiator
single DNA replication without repair
formation of stable, heritable changes in cell DNA

Question 16

2 classes of mutations

Answer 16

point and frameshift

Question 17

what is promotion

Answer 17

change in gene expression without change in DNA

Question 18

promotion is ______

Answer 18

reversible

Question 19

the promotion stage stimulates __________ in _________ cells

Answer 19

proliferation in both normal and mutated cells

Question 20

promotion enhances effect of genotoxic initiating agent by

Answer 20

establishing clones of initiated cells

Question 21

in promotion, a long delay is possible between

Answer 21

admin of initiating agent and promoting agent

Question 22

what is the final stage of the carcnogenesis process

Answer 22

progression

Question 23

in the progression stage, there is conversion of

Answer 23

benign preneoplastic lesions into a neoplastic cancer

Question 24

the conversion of benign preneoplastic lesions into a neoplastic cancer is the result of _______________________________ mediated by __________________

Answer 24

genotoxic events inducing chromosomal damage- aberrations and translocation
Mediated by increase in DNA synthesis and cell proliferation in the preneoplastic lesions (promotion stage)

Question 25

genotoxic means

Answer 25

Ability to damage DNA = mutations in critical genes = cancer

Question 26

majority of known human carcinogens are

Answer 26

genotoxic

Question 27

what is the effect fo nongenotoxic carcinogens

Answer 27

don’t damage DNA but alter balance between proliferation and apoptosis

Question 28

direct acting chemical carcinogens have ________ that __________

Answer 28

highly reactive electrophile groups
directly attack nucleophilic DNA groups/ proteins

Question 29

which type of carcinogens are more likely to cause a second form of cancer, usually leukemia

Answer 29

primary carcinogens

Question 30

what type of carcinogens must be metabolically activated

Answer 30

secondary/ indirect acting

Question 31

how are indierct acting carcinogens activated

Answer 31

endogenous metabolic pathways like CYP enzymes

Question 32

what are cocarcinogens

Answer 32

substances that ↑ carcinogenic potential by stimulating biotransformation of a certain substance

Question 33

what are promoters

Answer 33

suppress apoptosis, stimulate proliferation

Question 34

list 2 ways chemical carcinogens can mess with DNA

Answer 34

covalent bond formation
intercalation by forming noncovalent bonds

Question 35

most carcinogens are ___________ acting and _______( genotoxic/ nongenotoxic)

Answer 35

indirect
genotoxic

Question 36

adduct formation is common on _____ of adenine and _____ of guanine

Answer 36

6, 7 on adenine
2, 7, 8 on guanine

Question 37

Mutations may be induced by agents that interact with DNA _________ intercalating between 2 base pairs

Answer 37

VDWs forces

Question 38

insertion of flat planar rings between stacked double helical DNA =

Answer 38

frameshift mutation

Question 39

alkylated bases in DNA can

Answer 39

mispair with wrong base in DNA replication

Question 40

modifications on N ___ or ____ of purines can cause cleavage by DNA glycosylase

Answer 40

3, 7

Question 41

interaction with some carcinogens cause ________________ for better stability, altering transcriptability of certain genes

Answer 41

conformational transition of DNA

Question 42

what is the tired approach for genotixicity testing

Answer 42

in vitro
short term in vivo tests
long term in vivo carcinogenicity assays