Chemical carcinogenesis
12 important questions on Chemical carcinogenesis
Why is smoking deathly?
What is DNA adduct?
What kinds of carcinogens can be present in food?
- Naturally present carcinogens in plants (fytotoxins)
- Formed by micro-organisms present in decaying food (mycotoxins)
- synthetic carcinogens (dioxins)
- products formed during heating up food (pyrolytic and pyrosynthetic products) (BBQ)
- carcinogens formed from nitrite and other precursors in the stomach by low pH
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Methods for Detecting DNA Adducts
Why is aflatoxine B1 a very potent carcinogen?
Stages of Chemical Carcinogenesis?
Explain the classical carcinogenesis model
Initiation: gene mutation --> changed function of gene. No morphological changes yet.
Promotion: Circumstances are created in which cells are more susceptible for mutations or in which the initiated cells have a growth advantage. There are no mutations of karyotypic changes, promotion happens by interference with cellular signaling. This is a reversible process since no additional mutations occur.
Progression: karyotypic instability or instability by change of DNA-methylation occurs --> metastases, hyperproliferation and loss of control by cellular environment.
Explain the non-classical model of carcinogenesis
- The genotoxic model gives direct binding to DNA and causes genomic damage, one carcinogenic molecule would thus be sufficient to cause a mutation.
- The non-genotoxic mechanism gives inflammation, immunosupression, ROS, receptor activation and epigenetic silencing. The carcinogen thus gives its effect by binding to molecules other than DNA and causes an altered signal transduction.
Why is benzo[a]pyrene (BP) a genotoxic human carcinogen?
What are two examples of ABC family proteins that are transporters?
Explain the non-genotoxic model of carcinogenesis in detail
Epigenetics are also involved in chemical carcinogenesis. Epigenetics is are alternate phenotypic states that are not based in differences in genotype and which are potentially reversible. In general they are stably maintained during cell division. These changes are often histone modification, acetylation and DNA methylation.
Explain how extrapolation is used in non-genotoxic (with a threshold) cancer studies
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