Saturday, April 8, 2017

Azathioprine: how dangerous is it? Does severe DNA damage carry a risk of cancer? no need for a carcinogen or a virus

Viruses open up DNA and either methylate or demethylate it while a carcinogen binds the viral polymerase so the hosts polymerase is free to function....causing cancer.

Does Azathioprine remove the need for a virus or carcinogen? Does the severe breakage of DNA cause Demethylation to the point that Hervs become activated?

Since Azarthioprine involves demethylaltion only those aggressive cancers are seen? Is this true? I am suggesting that it is not just the immunosuppression that causes the cancer but the drug itself.

PTLD (increased lymphoma)
http://www.cancertherapyadvisor.com/lymphoma/ptld-an-unfortunate-complication-after-transplant/article/268067/

Azathioprine (AZA) is an inhibitor of purine synthesis and has been used as an immunosuppressant since 1960s.[] Mycophenolate mofetil (MMF) is a more selective inhibitor of purine, 

Azathioprine produces high levels of 6TG (which increased skin cancer)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426755/

6TG and demethylation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430383/

6-thioguanine (6TG), which induces DNA double-strand breaks (DSB) that are repaired 

DNA repair stimulates demethylation
http://www.sciencedirect.com/science/article/pii/S0301468108000054

Herv-E and transplants (supports demethylation awakening )

Zygote - demethylation- Blastocyte- methylation- Epiblast (pluripotent cells)
       awakens Herv K                                Herv H

Epiblast  -demethylation  - PGCs  -  methylation -Fetus
                    Herv E                              Herv W

viruses: HPV/flavivirus    Herpes/ polyomaviruses/retroviruses
                   demethylation                     methylation

(note that " only nuclear viruses cause cancer" is a current hypothesis)

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