1-32 Carcinogenesis

Question 1

driver mutation

passenger mutations

Answer 1

promotes cell growth

dont drive the cancer but are aquired along the way

Question 2

carcinogens

procarcinogens

Answer 2

chemical, physical, radiation, oncogenic viruses; electrophilic carcinogens initiate cell DNA damage

require metabolic activity in order to become carcinogens: ex: polycyclic aromatic hydrocarbons

Question 3

alkylating agents

Answer 3

used in chemotherapy but increases risk of future secondary cancers, mainly leukemia/lymphoma

has a nitrogen and lone pair, self cyclize and becomes eletrophillic, reacts with DNA nitrogren bases and makes an adduct, will stay in place until DNA replication causing errors; also will cross link DNA strands causing mutations and errors

ex: nitrogen mustards

Question 4

2 stage skin carcinogenesis model

Answer 4

1. initiation
2. promotion —-> progression

initiation: DNA damage in critical gene, rapid, irreversible, results in altered cell that could give rise to tumor if it proliferaties
promotion: cell prolif, reversible, promoter enhances cell prolif, does not alone affect DNA directly

progression: genetic mutations accumulate, invasive metastatic tumor
requires both steps! causes a DNA lesion when exposed to promotor and then a promoter encourages cell growth

Question 5

direct-acting carcinogens

Answer 5

electrophilic bind to nucleophilic DNA to form carcinogen-DNA adducts

ex: Nitrogen mustards, cancer chemotherapeutic agents, highly carcinogeneic, increase risk of secondary cancers (leukemias 15 years after treatement)
ex: alkylating agent: has a nitrogen and lone pair, self cyclize and becomes eletrophillic, reacts with DNA nitrogren bases and makes an adduct, will stay in place until DNA replication causing errors; also will cross link DNA strands causing mutations and errors

Question 6

The Ames test

Answer 6

try to grow bacteria that cannot normally synthesize histidine on a agar without histidine, and you grow on agar with different mutagens mixed in to see if the bacteria interacting with the mutagen will acquire a mutation and allow them to grow by now being able to synthesize histidine

test for mutagenicity of various carcinogens

Question 7

indirect acting carcinogens

Answer 7

ex: cigarette smoke

benzoapyrene activation of formation of DNA adduct, metabolism of the smoke compound in cells forms an intermediate that can form DNA adduct (indirect acting carcinogen)

can mutate important growth control genes, P53 common

phenols, catecols in cigarette smoke promote proliferation

Question 8

Aspergillus mycotoxins

aflotoxin B1

Answer 8

aspergillus produce aflotoxin b, a common contaminant of grains and peanuts

probable factor in the high incidence of hepatoceullular carcinoma in africa and asia, these carcinoms that arise in high-aflatoxin areas contain a signature p53 mutation

forms DNA adduct in specific position of p53