Estrogen as a Carcinogen in Women & Men w/ researcher Eleanor Rohan, PhD
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//Today’s Show //
Eleanor Rogan, PhD has been studying chemical carcinogens for over 30 years.
Today she explores how improperly metabolized estrogens can cause cancer; specifically when they’re metabolized to the Catechol estrogen quinone.
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01:34 In Nebraska, fracking is an issue as is the Keystone Pipeline. A spill would likely go into the Ogallala aquifer which provides water to multiple states.
06:18 Estrone is E1. Estradiol is E2. They convert back and forth.
06:55 Catechol estrogens can be methylated.
07:18 Catechol estrogens are an endogenous carcinogen.
08:32 P450 1B1 is dangerous in the number 4 position in the molecule. It creates a quinone and is highly reactive with DNA.
10:40 A study revealed that women with ovarian cancer have higher levels of estrogen DNA adducts than women who do not have ovarian cancer.
11:03 They looked at the polymorphic variations in 2 enzymes. One was a variant that made cytokine P450 1B1 more active. The other was a variant that made catechol-o-methyltransferase, a protective enzyme, less active. Women with particular varients were 3 times more likely to have ovarian cancer. Those other varients were six times more likely to have ovarian cancer.
13:27 When our COMT is functioning normally, we make the catechol estrogen and put a methyl group on it. It cannot from a quinone. Lower levels of quinones means you have lower levels of adducts.
13:50 If your catechol-o-methyltransferase is not working well, your catechol estrogen can go on to become a quinone and react with DNA.
16:18 Dopamine is the only other molecule that goes through this kind of metabolism; however, it is pH dependent.
18:03 It would cost a few $100,000 to determine if researching dopamine quinones in Parkinson’s was the right track for something useful. Funding is not available.
19:25 Dopamine quinones make analogous DNA adducts.
20:36 Adducts are analogous to taking a step off the DNA ladder.
27:02 Men with prostate cancer have high levels of estrogen DNA adducts. It may be that prostate cancer is initiated by estrogens and promoted by testosterone.
32:22 Studies of HRT show evidence is that the problem is not with the estrogen, but with the synthetic progestin.
35:25 Dr. Rogan’s research with sulforaphane showed it not to be as effective as it was hoped.
36:08 A study of resveratrol and n-acetylcystine taken twice a day, showed that after 3 months, adduct levels were lowered significantly statistically.
43:20 Dr. Rogan is studying Fuch’s eye dystrophy. These cells make many estrogen DNA adducts.
48:46 The formation of estrogen adducts may be a fundamental mechanism of disease. It is probably involved in a variety of things besides cancer.
54:57 Promising research on estrogen carcinogenesis is not funded/supported.
01:00:22 Initiation of cancer by estrogens does not require the estrogen receptor.