Chemical carcinogens Flashcards Preview

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Flashcards in Chemical carcinogens Deck (34)
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1
Q

what is 3,4-benzypyrene oxidised by and to

A

glutathione s-transferases to 7,8-epoxide metabolite

2
Q

where is p53 highly active

A

malignant cells

3
Q

what does error-prone DNA replication require

A

DNA polymerases delta and epsilon

4
Q

Which cytochromes biotransforms polycyclic aromatic hydrocarbons (4)

A
  1. P450
  2. 1A1
  3. 1A2
  4. 1B1
5
Q

what is the formation of epoxides catalysed by

A

UDP-dependent glycuronosyl transferases

6
Q

what is the chemically structure of polycyclic aromatic hydrocarbons

A

carbon and hydrogen arranged into aromatic rings

7
Q

what do all major carcinogens in this group contain

A

bay region

8
Q

what does the K region contain

A

higher electron density

9
Q

what is a imbalance between K and L regions suggested to cause

A

carcinogenicity

10
Q

what can epoxides form

A

K regions

11
Q

what occurs during nucleotide excision repair

A

repairing of DNA damage with low fidelity

12
Q

where are polycyclic aromatic hydrocarbons in the environment from

A

anthropogenic sources

13
Q

where is the aryl hydrocarbon receptor found

A

nucleus of hepatocytes

14
Q

what excretes polycyclic aromatic hydrocarbons

A

kidneys

15
Q

what do the bay regions bind with in particular

A

NH2 group of guanine

16
Q

what kind of molecules are PAHs

A

planar molecules

17
Q

what do most PAHs contain

A

phenanthrene nucleus

18
Q

where in the plenanthrene moiety is the bay region located

A

C4 to C6

19
Q

what increases carcinogenicity

A

addition of other planar ring systems to C6C7

20
Q

two types of cancer

A

benign and malignant

21
Q

three most common classifications of cancer and where do they develop

A
  1. carcinomas - epithelial cells
  2. sarcomas - bone and muscle
  3. leukaemia - blood
22
Q

five classes of chemical carcinogens

A
  1. alkylating agents
  2. nitroso compounds
  3. azo dyes
  4. aromatic amines
  5. polycyclic aromatic hydrocarbons (PAHs)
23
Q

when are PAHs generated

A

whenever organic materials are burned

24
Q

when was the association between cancer and PAHs first noted

A

in 1775

25
Q

what do the diol-epoxides of 3,4-benzypyrene normally bind to?

A

guanine residues of DNA

26
Q

what correlations were found between carcinogenic activity and electron density

A

high electron density resulted in greater carcinogenic activity

27
Q

what do PAHs form and what is this reaction catalysed by?

A

K-region epoxides catalysed by cytochrome p450

28
Q

why are epoxides dangerous?

A

they react directly with DNA forming mutagens and carcinogenic activity

29
Q

what became clear by the 1970s regarding epoxides

A

that non-K-region exoxides could exist

30
Q

how do the diol-epixodes of 3,4-benzpryene bind to guanine

A

covalent bond is formed between C10 of benzo(a)pyrene and the exocyclic 2-amino

31
Q

why does binding of PAH cause damage to DNA

A

repair is not always accurate leading to point mutations

32
Q

what do 10% of human tumours contain

A

mutations of ras genes

33
Q

what is different about oncogenic p21

A

it has lost its GTPase activity = constant signalling for growth

34
Q

how to measure PAH exposure

A

electrophilic metabolites of PAHs form covalent adducts with albumin and haemoglobin which can then be assayed