carcinogensis Flashcards
Bcl2 overexpression translocation
tr(14, 18), so translocates Bcl2 with Ig gene
What needs to happen for tumor to occur?
Initiator followed by promoter (regular sustained exposure)
Steps of carcinogenisis
tumor initiation (DNA damage or epigenetic changes) , tumor promotion (selective clonal expansion), malignant conversion, and tumor progression (metastasis potential)
What are chemical initiators like?
electrophilic (metabolite of drug Nzms), changes in DNA metabolism
Types of initiators?
direct: no transformation, alkylation and acylation
Indirect: metabolic conversion required
Features of initiators?
DNA adduct forms, DNA damage, and tissue specific
How is carcinogenic potential of initiators affected?
inherent reactivity, metabolite activation (CYP450) and inactivation (gluthathione-s-transferase) reactions, genetic polymorphisms
What do initiators do?
activate oncogene, alter apop pathway, inact of tumor suppressors, inact. DNA repair mech.
What do promoters do?
bind cell surface–cell proliferation, specific to tissue as interact with receptors
Types of general categories
specific promoters-interact with Receptors or in target cells defined tissues
Non-specific promoters: alter gene expression–w/o presence known receptors
Effects of promotors?
Maximal and threshold
mechanism of promoters
Epigenetic- change in gene exp. but no DNA damage; promoters induce cell prol. (mitogenic) (TPA-Phorbol esters)
less GF requirements and less responsive to inhibitors
Molecules for promoters mech
ROS, Redox metals, Polycylic aromaic compounds, (oxidative stress)
Eg. of Chemical carcinogen
Direct acting alkylating agents (guanine groups affected)–chemotherapy drugs
What do polycylcic hydrocarbons do?
initiators and promotors, metabolized by cyp450, electrophilic epoxides (cigeratte smoke have initiators and promotors, animal fat), eg. vinyl chloride
Chemical carcinogen: What do N-Nitrosamines do? Where is it?
CYP450, carbonium ion, indirect acting carcinogen; diet, tobacco smoke, drinking water (Nitrates are in water and vegetables), smoked meats, bear and whisky)
Chemical carcinogen: What do aromatic amine and azo dyes do?
Naptheline, metabolite of cyp450, increased incidence of urothelial cancer and field effect
What is field effect?
if exposed to entire epithelium, then cancer is likely to develop in the area (secondary tumor development)
Chemical carcinogen: What does Aflatoxin B1 do?
from Aspergillus flavus (indirect carcinogen) epoxides bind to guanine in TP53–mutations; in improperly stored grain and peanuts (Hepatocellular cancer)
What cancer does alcohol cause?
esophageal squamous, hepatocellular, Head and neck
What cancer occurs due to arsenic exposure?
Lung squamous, skin, liver angiosarcoma; from cigeratte smoke
What cancer occurs due to abestos exposure?
lung and mesothelioma (lung more though)
What cancer occurs due to Ni, Chromium, Si, and Be exposure?
Lung and its occupational exposure
What does UV radiation contribute to cancer?
UVB: DNA adducts, direct damage, pyrimidine dimers; and UVA: oxidation (indirect DNA damage), free radicals
