ddt 4

Question 1

the physical mutengens include:

Answer 1

• Uv light - ioniznzing radiation
  causes: dimerisation of pyrimdide , hydration of cytosine and causses direct damage to the dna by the production of reactive oxygen species
• x rays and gamma rays - travels through the cell without collisions and stand breaks if they collide w/ dna
• particle radiation as alpha and beta which impacts the nuclear dna and causes breaks in the dna

Question 2

— are negative regulators of cell growth and commonly inactivated in cancer cells

Answer 2

tumor supressor

Question 3

– found in normal cells and are involved in positive regulation of cell growth but are often mutated in cancer cells

Answer 3

proto-ongogenes

Question 4

the process of carognsies involves:

Answer 4

1- initiation: genetic alteration or mutation of one or more cellular genes controlling the regulatory pathway
2- promotion: selective growth enhancement induced in the ignited checks and its progeny by the continuous exposure to the promoting agents
3- transformation : the preneoplastic cells transforms and expresses magian phenotype
4- progression : expression of malignant genotype and acquire aggressive characertsics as: genomic instability, uncontrolled growth, and metatsiss

Question 5

—- are intrinsically reactive and form adducts with the dna without the metabolic modification

Answer 5

direct carigones
as: nitrogen mustard, methyl nitrosourea

Question 6

—- require metabolic activation before damaging the dna by the covalent adduct formation or reactive oxygen species

Answer 6

procargones
becomes proximate carigoens and then ultimate cargoes which forms adducts as: benzo(a) pyrene , aflatoxin , dimethlnitroamine

Question 7

mutegens and carcinogens causes damage to the dna by :

Answer 7

1- covalent adduct formation as:
- alkylation
- deamination
- formation of bulky aromatic type
- dimerisation
2- oxidative damage

Question 8

in bulky aromatic adducts:
the first chemically identified carcinogens were —

Answer 8

• polycyclic aromatic hydrocarbons
• they are very common envriomental contaminants
• number o fused bene rings ( CHECK STRUCTURE )
• formed by the incomplete combustion of fossil fuel ad vegetable matter
• chemically inert so it require metabolic activation by cytochrome P450
• example of the bulky aromatic: bees(a) pyrene

Question 9

activation of benzodiazepines(a)Byrne and adduct formation

Answer 9

1 – BP is converted to Benzo(a)pyrene-7,8-diol by P450 and Epoxide hydrolase
2 – P450 adds another epoxide group to positions 9,10.
3 – Diol epoxide can undergo cleavage of C-O bond of epoxide at position 10 and form carbocation intermediate (electrophile)
4 – Ultimate carcinogen targets N-2 deoxyguanine residues which can perform nucleophilic attack of carbocation

Question 10

Aflatoxin B1 targets —-

Answer 10

• N7 on guanine
• found in soil and decay vegetation
  -can contaminate food sources
• leads to liver cancer
  -Procarcinogen  Aflatoxin B1 epoxide (ultimate carcinogen).
  Targets N7 nitrogen in guanine when forming adduct

Question 11

— attaches small alkyl groups into the nucleophilic sites to form dna adducts as dimethylnitroamines and nitrosamines

Answer 11

• alkylating agents

Question 12

Dimethylnitrosamine and other nitrosamines are products of —- and are examples of —- they are procarogenes which produces —-

Answer 12

• industrial bi-products and tobacco smoke and cured meat
• alkylating agents
• reactive diazonium and carbonic ions

Question 13

nitrous acid HNO2 is a —- which converts cytosine into – and adenine into — and guanine into —
the hydrogen bonding potential of modified bases is altered resulting in —-
hypoxathine can pair with – and causes mismatch

Answer 13

• demainating agent
• auricle
• hypoxanthine
• xanthine
• mismatch
• cytosine

Question 14

— is the Removal of errors due to adduct and oxidative damage

Answer 14

excesion repair

Question 15

is the removal of deamination and small deletion & insertion damage

Answer 15

mismatch repair

Question 16

Removal of methyl groups from bases without removal of base is

Answer 16

direct reversal repair

Question 17

Removes a variety of base damages such as 8-oxo-guanine, deaminated bases and methylated bases.

Answer 17

• base excision repair
• 8-oxo-gunaine is from reactive oxygen species and is repaired by dna glycolyses as it flipped out of the double helix and cleaveged into the n-glycosidic bond and creates an absasic site

Question 18

Repairs DNA with bulky adducts
Adducts result from UV damage or electrophilic aromatic mutagens such as Benzo(a)pyrene —

Answer 18

nucleotide excision repair
( Recognition of the damage initiates removal of a short single-stranded DNA segment containing damage.
The undamaged complementary strand is left intact
DNA polymerasecomplementary strand used as a template to synthesize replacement sequence.
DNA ligase completes repair process.)