Cancer: Mechanisms of DNA Damage Flashcards

1
Q

list 3 types of DNA damage that lead to carcinogenesis

A
  • broken hydrogen bonds turning into covalent bonds
  • double stranded breaks (translocation mutations)
  • DNA adduct (chemical clusters of atoms that react with DNA)
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2
Q

Some chemical carcinogens are _____ carcinogens whilst others require some form of _______ _______.

A

direct

metabolic activation

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3
Q

chemical carcinogens were once used as

A

manufacture of dyes

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4
Q

chemical carcinogens aromatic amines and aminoazo compounds contain

A

amino and azo groups which vary strongly carcinogenic and non-carcinogenic

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5
Q

polycyclic aromatic hydrocarbons are

A

naturally occurring products from the incomplete combustion of nearly any organic compound (coal, tar, oil, meat, tobacco)

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6
Q

polycyclic aromatic hydrocarbons are defined by their

A

polycyclic ring structure

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7
Q

list 2 characteristics of N-nitro compounds

A

-industrial chemicals
-nitrates and nitrites are not carcinogenic but are converted to nitrosamines in the gastrointestinal tract

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8
Q

alkylating agents are not defined by their chemical structure but by their

A

reactivity (ability to join a chemical group to another molecule)

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9
Q

what is one mechanism of chemical carcinogens?

A

methylation

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10
Q

describe methylation mechanism

A

a methyl group is added to a DNA base -> incorrect base pairing occurs -> subsequent base pairing now forms a normal pair that become permanent mutations and cannot be repaired

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11
Q

how does UV damage DNA

A

by creating pyrimidine dimers in adjacent thymine’s. if not repaired it can cause improper base pairing during replication and downstream a permanent mutation that is formed and is capable of indefinite replication

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12
Q

How does benzo[a]pyrene distort the double helix molecule?

A

benzo[a]pyrene interacts with cytochrome p450 in the liver creating an intermediate with an epoxide group. This reacts with guanine in DNA

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13
Q

how does phorbol ester lead to cell proliferation

A

binding of external signal molecule leads to activation of phospholipase C -> phospholipase C cleaves membrane lipid PIP2 to produce DAG -> DAG activates protein kinase C triggering events that lead to cell division

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14
Q

what determines the carcinogenic ability of phorbol esters?

A

the number and position of side chains
(alterations reduces affinity for binding PKC)

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15
Q

what are the 2 ultimate outcomes of pathway mutations?

A
  1. cell proliferation in excess
  2. inhibit apoptosis
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