[futurepilot]

The object of this article is to review briefly the preclinical and clinical safety of some antiestrogens. Tamoxifen, toremifene, droloxifene, and idoxifene are polyphenylethylene antiestrogens, whereas the pure antiestrogen, ICI 182,780 or faslodex, as well as raloxifene, is of a different structure. Tamoxifen has been shown to be genotoxic in several studies. It induces unscheduled DNA synthesis in rat hepatocytes and micronuclei in MCL-5 a cells in vitro. Tamoxifen also induces aneuploidy in rat liver in vivo and chromosome aberrations and micronuclei in mouse bone marrow. Toremifene has also shown to be genotoxic, but to a far lower extent, by inducing micronuclei in MCL-5 a cells in vitro and by inducing aneuploidy in rat liver in vivo. Tamoxifen has been shown to be hepatocarcinogenic in the rat in at least four independent long-term studies. The initiation of tumors in the rat is the result of metabolic activation by cytochrome P450 isoenzymes to an electrophile(s) that binds irreversibly to DNA. The other antiestrogens have not been shown to be carcinogenic in rodents. In several independent clinical studies, the risk of endometrial cancer has increased among tamoxifen-treated women. After reviewing the available data, the International Agency for Research on Cancer concluded that there was sufficient evidence to show that tamoxifen is a class I human carcinogen. The increased risk for endometrial cancer occurs predominantly among women who are 50 years old or older and who have been treated with tamoxifen. It is not yet clear whether the uterine tumor formation is a result of genetic mechanisms, analogous to those seen in the rat liver or due to the estrogen agonist action of tamoxifen. However, the other antiestrogens with a more or less similar intrinsic estrogenic potential have not been shown to be carcinogenic in humans.


Pirkko Hirsimäki, PhD,**Department of Pathology, Turku University Central Hospital, BioCity.

Annukka Aaltonen, MSc,*†*Department of Pathology, Turku University Central Hospital, BioCity, †Hormos Medical Ltd., Pharma City, Turku, Finland.

Eero Mäntylä, MSc‡‡Brion Scientific Ltd., Unit for Independent Medical Writing, Piispanristi.

[ReaperX]

The crazy thing too is I bet there are a lot of people out there who do not know this....................

[futurepilot]

Thats what i was thinking. I didn't find any good articles posted anywhere on here about it so i figured i would put this one up.

[pistonpump]

well i guess im getting cancer then.

[ezza]

unless you have a vagina i don't think you will get endometrial cancer....

[ezza]

probably the reason people don't know of this or it hasn't been posted before is that it's probably not relavant considering we only use the stuff in short bursts for pct and are not women... i'm really suprised that no one else has picked up on this....

[dmangiarelli]

Originally Posted by futurepilot

Tamoxifen has been shown to be hepatocarcinogenic in the rat in at least four independent long-term studies. The initiation of tumors in the rat is the result of metabolic activation by cytochrome P450 isoenzymes to an electrophile(s) that binds irreversibly to DNA.

I thought this was much more interesting than the part you highlighted. The question would be were these studies done on rats that ingested high doses or low doses?

[BodyWizard]

...and for how long???

[Rodja]

And how is this applicable knowledge for PCT use??

[dmangiarelli]

Originally Posted by Rodja

And how is this applicable knowledge for PCT use??

That Tomoxifen is hepatocarcinogenic?

[Rodja]

Originally Posted by dmangiarelli

That Tomoxifen is hepatocarcinogenic?

It says in long-term usage in rats. What defines "long-term," what is the equivalent dose, and when where they conducted?

It is not a secret that Tamoxifen is hepatoxic, but this abstract is much too vague to draw any conclusions relevant to out common usage. That is one of the downfalls of reading abstracts as opposed to studies.

[dmangiarelli]

Originally Posted by Rodja

It says in long-term usage in rats. What defines "long-term," what is the equivalent dose, and when where they conducted?

It is not a secret that Tamoxifen is hepatoxic, but this abstract is much too vague to draw any conclusions relevant to out common usage. That is one of the downfalls of reading abstracts as opposed to studies.

I agree. There is no dosage or time information so you really can't draw any conclusions per se. It's just more information ...

Most of these studies (and this is a compendium of studies) give ridiculous amounts of the drugs to the rats (something we would never ingest) and so it causes these effects. So it leaves a lot of questions. The stuff about Torem being genotoxic was also interesting.

"Tamoxifen has been shown to be genotoxic in several studies. It induces unscheduled DNA synthesis in rat hepatocytes and micronuclei in MCL-5 a cells in vitro. Tamoxifen also induces aneuploidy in rat liver in vivo and chromosome aberrations and micronuclei in mouse bone marrow." This also caught my eye ...

Does it have anything to do with PCT? That is up to whoever uses it ...

[Rodja]

Originally Posted by dmangiarelli

I agree. There is no dosage or time information so you really can't draw any conclusions per se. It's just more information ...

Most of these studies (and this is a compendium of studies) give ridiculous amounts of the drugs to the rats (something we would never ingest) and so it causes these effects. So it leaves a lot of questions. The stuff about Torem being genotoxic was also interesting.

"Tamoxifen has been shown to be genotoxic in several studies. It induces unscheduled DNA synthesis in rat hepatocytes and micronuclei in MCL-5 a cells in vitro. Tamoxifen also induces aneuploidy in rat liver in vivo and chromosome aberrations and micronuclei in mouse bone marrow." This also caught my eye ...

Does it have anything to do with PCT? That is up to whoever uses it ...

It is all relevant information, but this is another reason that support supplements should be used throughout PCT. The truth is that we will never really know because there will most likely never be a study on PCT lengths/dosages of SERMs.

[futurepilot]

I put this up because here are some other class 1 carcinogens.

Aflatoxins (naturally occurring mixtures of)
4-Aminobiphenyl
Arsenic and arsenic compounds1
Asbestos
Azathioprine
Benzene
Benzidine
Beryllium and beryllium compounds2
Chlornapazine (N,N-Bis(2-chloroethyl)-2-naphthylamine)
Bis(chloromethyl)ether
Chloromethyl methyl ether
1,4-Butanediol dimethanesulfonate (Busulphan; Myleran)
Cadmium and cadmium compounds2
Chlorambucil
Methyl-CCNU (1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea; Semustine)
Chromium(VI) compounds2
Ciclosporin
Cyclophosphamide
Diethylstilboestrol
Dioxin
Epstein-Barr virus
Erionite
Ethylene oxide
Etoposide in combination with cisplatin and bleomycin
Formaldehyde
Gamma radiation
Gallium arsenide
Helicobacter pylori (infection with)
Hepatitis B virus (chronic infection with)
Hepatitis C virus (chronic infection with)
Herbal remedies containing plant species of the genus Aristolochia
Human immunodeficiency virus type 1 (infection with)
Human papillomavirus type 16
Human papillomavirus type 18
Human T-cell lymphotropic virus type I
Melphalan
Methoxsalen (8-Methoxypsoralen) plus ultraviolet A radiation
MOPP and other combined chemotherapy including alkylating agents
Mustard gas (Sulfur mustard)
2-Naphthylamine
Neutron radiation
Nickel compounds2
Oestrogen therapy, postmenopausal
Oestrogens, nonsteroidal1
Oestrogens, steroidal1
Opisthorchis viverrini (infection with)
Combined forms of hormonal contraception (those containing both estrogen and a progestogen)3
Sequential forms of hormonal contraception (a period of estrogen-only followed by a period of both estrogen and a progestogen)
Phosphorus-32, as phosphate
Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
Radioiodines, short-lived isotopes, including iodine-131, from atomic reactor accidents and nuclear weapons detonation (exposure during childhood)
Radionuclides, α-particle-emitting, internally deposited4
Radionuclides, β-particle-emitting, internally deposited4
Radium-224 and its decay products
Radium-226 and its decay products
Radium-228 and its decay products
Radon-222 and its decay products
Schistosoma haematobium (infection with)
Silica , crystalline (inhaled in the form of quartz or cristobalite from occupational sources)
Solar radiation
Talc containing asbestiform fibres
Tamoxifen
2,3,7,8-Tetrachlorodibenzo-para-dioxin
Thiotepa (1,1',1"-Phosphinothioylidynetrisaziridine)
Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium-232 dioxide
Treosulfan
Vinyl chloride
X-Radiation



So how long? What dose? Ill hook you up with some mustard gas...let me know how it goes.