Hello - you ask a relatively large question - here is a general
overview:
1) Environmental and genetic factors predisposing to cancer - Cancer
is the result of cells loosing their ability to grow appropriately
within the organism as a whole. This is the result of damage to genes
within the cancer cells which regulate normal growth. Environmental
insults can result in direct damage to genes which are involved in
regulating cell growth, thus producing cells which grow abnormally.
Genetic factors may also play a role - generally, a person has two
copies of each gene - however, if one of the copies that is inherited
is non-functional, then this person is at risk for inactivation of the
single remaining gene - if this gene is involved in the regulation of
growth, this puts them one step closer to the development of cancer.
Environmental factors and cancer:
Radiation can increase the risk of cancer by directly damaging the DNA
in a cell and/or by damaging rapidly growing cells (such as skin,
stomach lining, etc) which requires more cell growth to replace, thus
allowing for more incidental DNA damage and increasing the risk that
some of the newly grown cells will be cancerous.
A very long report on radiation and cancer:
http://www.rerf.or.jp/eigo/archives/cr3-96.htm
A nice overview of the biological effects of radiation:
http://www.triumf.ca/safety/rpt/rpt_4/node1.html
Carcinogens (compounds which have been shown to cause cancer) can
produce cancer, in general, via two different mechanisms. They can
either damage the DNA or cause cells to proliferate in the presence of
damaged DNA (normally cells will not copy themselves if their DNA has
been damaged).
DNA damage may be the result of adduct formation (adding something to
the DNA):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=9307842&dopt=Abstract
or it can be the result of intercalating agents (compounds which
"slip" into the double helix and prevent accurate copying of the DNA):
A somewhat esoteric page on this topic:
http://www.ncsa.uiuc.edu/News/Access/Stories/dynamicdna/dynamicDNA2.html
Growth promoting compounds are typified by PMA:
A nice review of the effects of carcinogens:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11082709&dopt=Abstract
Genetic factors which predispose to oncogenesis can be roughly grouped
into two categories, tumor promoters (oncogenes) and tumor
suppressors. Tumor promoters are genes which when mutated tend to
cause cancers while tumor suppressors normally block oncogenesis, but
when mutated, are unable to perform this role.
Oncogenes include such notables as Ras, Jun, Src, Bcl-1, Bcl-2 and
others:
http://www.ohsu.edu/cliniweb/G5/G5.275.740.791.html
Tumor suppressors include P53, Rbl, FAP and others. A nice short
review of tumor suppressors:
http://www.hhmi.org/news/vogelstein.html
A nice article in the New England Journal of Medicine describing the
environmental and genetic factors found to be linked to cancer in a
large study of twins seems to indicate that environmental exposure,
versus genetics, plays the largest role:
http://content.nejm.org/cgi/content/short/343/2/78
2) Mechanism of transformation from a normal cell to a cancerous cell
- The classic model of oncogenesis was worked out by Bert Vogelstein
and his colleagues who were investigating colon cancer. The scheme
goes as follows: cells first begin to over-proliferate (hyperplasia)
but are otherwise mostly normal in appearance and function (this
likely results from exogenous tumor promoting substances, or damage to
oncogenes which then promote growth without proper stimulus). The
cells then accumulate further damage as they proliferate until they
begin to invade the surrounding normal tissue and no longer look like
they should (dysplasia). This invasive growth continutes until the
tumor makes contact with lymph or blood vessels at which point cells
can flake off and seed other locations in the body (metastasis) - this
likely requires further mutations that allow the tumor to grow in
locations in which it's cell type are not normally accepted.
Additionally, large tumors may accumulate the mutations necessary to
cause blood vessel growth into the tumor - a necessary step for large
tumor formation.
In particular, see slides 8-10, but the whole presentation is very
good as well:
http://www.med.umich.edu/lrc/coursepages/M1/humangenetics/HG501_CALx_21.pdf
A heavy-on-the-math article detailing a model of oncogenesis:
http://ejde.math.swt.edu/conf-proc/10/a4/ahangar.pdf
Please let me know if you need more information.
synarchy
Search strategy for references:
oncogenesis mechanisms
oncogenesis radiation
oncogenesis carcinogen
carcinogenesis mechanism
multi-stage model of tumorigenesis |
,
0 Comments
)