Carcinogens

Question 1

what percentage of cancers are caused by environmental causes

Answer 1

80%

Question 2

what are the 5 groups of carcinogens

Answer 2

alkylating agents
aromatic amines
azo dyes
nitroso compounds
polycyclic aromatic hydrocarbons

Question 3

what are the specific types of environmental causes of cancer

Answer 3

toxins
UV/ionising radiation
oncogenic viruses
man-made carcinogens

Question 4

how many forms of PAHs are produced and how

Answer 4

700 by conbustion of hydrocarbons

Question 5

how are we exposed to pahs

Answer 5

diet, inhilation, lipophilic absorption through skin

Question 6

why do pahs bioaccumulate but not biomagnify

Answer 6

due to enzymatic detoxification

Question 7

why is persistence of pahs limited

Answer 7

photodegradation

Question 8

what was the first pah to be discovered

Answer 8

3,4-benzopyrene

Question 9

what is the structural simalarity between the most potent chemicals

Answer 9

phenanthrene nucleus

Question 10

what is the K region of the phenanthrene ring

Answer 10

the area of highest electron density

Question 11

what property of the K ring allows interaction with DNA

Answer 11

planar

Question 12

what name is 3,4-benzopyrene also known by

Answer 12

benzo-a-pyrene

Question 13

what did pullmans electronic theory (1950) show

Answer 13

link between K region and carcinogenicity

Question 14

what was thought to be important in carcinogenicity and what was proven otherwise

Answer 14

L:K:M balance of electron densities

found its actually the active metabolites which are carcinogenic

Question 15

who first observed that the metabolites were in fact the carcinogens by putting benzopyrene but not the parent compounds on mice skin

Answer 15

elizabeth miller (1950s)

Question 16

who linked DNA binding to carcinogenicity and in which decade

Answer 16

Brooks and Lawley 1960s

Question 17

which cytochromes produce 7,8-epoxides of the K region

Answer 17

chytochromes p450 1A1 1A2 1B1

Question 18

what are the three methods of epoxide degradation

Answer 18

hydrolases convert it to a trans7,8- diol
glutathione peptide conjucation
spontaneous isomerisation to phenols

Question 19

what percentage of k region epoxides are left after to bind to DNA

Answer 19

5%

Question 20

are diol products more or less toxic

Answer 20

more

Question 21

which trans-diol epoxide was found to bind DNA to a greater extent than 3,4-benzpyrene

Answer 21

7,8-dihydrodiol

Question 22

what percentage of epoxides form above the ring (+ enantomer)

Answer 22

98%

Question 23

what is Cyt p450 also known as

Answer 23

CYPs

Question 24

what is the 7,8-diol produced by the mitochondiral epoxide hydrolase next converted to

Answer 24

7,8-diol-9,10-epoxide

Question 25

which form + or - is the diol in

Answer 25

-

Question 26

which enatomer is thought to be the ultimate carcinogen

Answer 26

the (+) 7,8-diol-9,10-epoxide

Question 27

whih residue to the diol epoxides mainly bind

Answer 27

guanine

Question 28

why will the epoxide ring open to form an electrophilic carbinium ion at C10

Answer 28

the ring is strained

Question 29

which atom does the epoxide bind

Answer 29

NH2 amine or N7

Question 30

what 4 step do pahs increase their metabolism

Answer 30

bind aryl hydrocarbon receptor in cytoplasm transported to nucleus using chaperones binds ARNuclear transporter heterodimer to bind to gene promoters increases synthesis of CYPs 1A1 1A2 1B1

Question 31

how does PAH binding cause carcinogenicity

Answer 31

causes damage to dna, repair not always acurate

Question 32

what are the critical genes in which mutations occur

Answer 32

proto onco genes (ras) and tumour supressor genes (p53)

Question 33

what percentage of tumours are caused by ras mutations

Answer 33

10

Question 34

which group of proteins do ras genes encode

Answer 34

p21

Question 35

what has been lost from oncogenic p21 and what is the resut

Answer 35

GTPase activity | constantly activated

Question 36

what is the role of p53

Answer 36

accumulates around damaged dna to allow repair to occur | induces apoptosis if repair fails

Question 37

what effect does muttion often have on p53

Answer 37

inactivation

Question 38

what can affect susceptibility to chemical carcinogens

Answer 38

expression of enzymes involved in metabolism of carcinogens mutations in enzymes involved in metabolism efficiency of dna repair

Question 39

what is usually the target organ of PAHs

Answer 39

liver

Question 40

what can be used as biomarkers of pah exposure

Answer 40

binding of electrophilic metabolites to proteins and dna

Question 41

what can be used to assay pah exposure

Answer 41

haemoglobin and albumin

Question 42

what are the effects of pahs aside from cancer

Answer 42

phototoxicity cardiovascular disease (atherosclerosis) foetal malformations disruption of development 3-6 years

Question 43

what are the adverse affects which arent cancer caused by

Answer 43

activation of aryl-carbon receptor

Question 44

how is damage to DNA detected

Answer 44

distortion of helix

Question 45

what isthe general process of dna repair

Answer 45

xp proteins provide scaffold, helicase unwinds dna, incisions by exonucleases remoce 27-29bp, dna polymerase delta and epsalon extends dna with high fidelity, dna ligase joins bases together

Question 46

under what circumstances are mismatches in dna not recognised and why

Answer 46

durin cell replication | uses low fidelity polymerase

Question 47

what is the common mutation caused by 3,4benzopyryne damage

Answer 47

g to t

Question 48

what is the common mutation caused by uv damage

Answer 48

c to t

Question 49

what are the 6 hallmarks of cancer

Answer 49

``` apoptosis evasion increased growth signals insensitivity to anti growth signals unlimited replication potential sustained angiogenesis tissue invasion and metastasis ```

Question 50

why are most cancers found in eptithelial cells

Answer 50

most exposure and most repair and mutations