Toxic Responses, cont.

Chemical Carcinogenesis, Cont.

Cancer induction involves at least two kinds of events:

1. an initiation phase.
2. 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

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