|Lecture Notes:: 30 March
© R. Paselk 2008
Toxic Responses, cont.
Chemical Carcinogenesis, Cont.
Cancer induction involves at least two kinds of events:
- an initiation phase.
- a promotion phase.
In general we can say
- Carcinogens appear to produce irreversible changes in a cell which with further factors may lead to the development of a tumor.
- Promotion involves cell proliferation and thus DNA replication.
Induction involves either a direct of indirect interaction with the genetic material such as:
- Mutations (Note that mutagens are not always carcinogens.)
- Obstruction to repair (e.g. Methylation of guanine at O6 is worse than at N7 because it is harder to repair.)
- Epigenetic, such as repression/derepression:
- alters cell growth, not inherited as DNA code.
- Immunological effects (Immune suppression etc.)
- For some carcinogens the correlation is better with RNA than DNA!
Cancer may often involve a failure of the repair/policing responses of the organism:
- Xeroderma pimentosum - DNA repair is prevented by loss of ligase.
- Severe immuno deficiency - tumors are allowed to grow and multiply because of lack of policing.
- "Boy in a bubble" autopsy at age eleven showed thousands of tumors in legs alone.
- AIDS/Kaposi's syndrome - rare cancer became quite common in this population.
Teratogenesis involves interference with normal development in utero. Stedman's Medical Dictionary (1972) defines teratogenesis as "The origin or mode of production of a monster" and/or "the production of malformations in the developing embryo."
Teratogenesis is highly complex, but one should expect that it should be easy to disturb such a complex and highly coordinated process as development, and that the timing of the disturbance should be important. (Timbrell 4th, Figures 6.22, p 239 and 6.23, p 240)
Last modified 30 March 2010
© RA Paselk 2001