President's Cancer Panel Meeting: Environmental Factors in Cancer, Transcript of Proceedings, Indianapolis, in, Oc by National Cancer Institute - HTML preview

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Key Points

Color differences between male and female frogs such as the Hyperolius puilus—found in Kenya—are hormonally regulated, such that exposure to exogenous estrogens will induce a

color change in the male that is typical of the female. Various estrogenic compounds, such as the endogenous steroid, estradiol; the synthetic steroidal estrogen, ethynyl estradiol; the

potent estrogen, DES; and the estrogen mimic, DDT; all induce color changes in this frog

species. These compounds, found to be estrogenic in the frog, are also known to be estrogenic in human breast cancer cells.

Atrazine—produced by Novartis—is an herbicide that has been used by corn growers for the

past 48 years in the U.S. Eighty million pounds are used annually, making it the number one

pesticide contaminant of ground, surface, and drinking water. It is used in more than 80

countries, but is illegal in Europe, where Novartis is based.

When researchers developmentally exposed the African clod frog to atrazine, it grew multiple ovaries in addition to its testes, transforming it to a hermaphrodite. Exposed North American leopard frogs were prone to growing eggs in their testes. Atrazine’s proposed mechanism of

action involves the induction of aromatase, which converts testosterone into estrogen and

results in feminization. Data supporting this hypothesis were published in the Proceedings of the National Academy of Sciences. Feminization effects similar to those seen in frogs have also been recorded in fish, turtles, alligators, chickens, and quail.

A study conducted in Columbia, Missouri in 2003 measured atrazine levels in the urine of

men and found higher levels in subfertile males—men characterized by low sperm count and

low semen quality—than in control males. Another study in California found that men who

apply atrazine have 24,000 times the chemical in their urine than the level associated with

subfertile men in Missouri. It is important to note that over 95 percent of the people who

grow food in California are Mexican or Mexican-American with lower-than-average life

expectancies.

Novartis conducted a study in rats in 1994 that showed a statistically significant association between atrazine and increases in estrogen-positive/sensitive mammary tumors. A separate

study in 2000 showed that atrazine reduced testosterone levels and sperm count in rats.

In 2001, Sanderson et al. showed that a human renal carcinoma cell line produces aromatase when exposed to atrazine—the same mechanism observed in frogs, fish, turtles, rats, etc. The

promoter that controls regulation of aromatase in the gonads of humans is the same in the

Indianapolis, IN

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October 21, 2008

gonads of all vertebrates (i.e., fish, reptiles, birds, mammals). Excess aromatase and estrogen production are associated with both mammary and prostate cancer in humans.

In 1997, a study showed that women in Kentucky whose well water was contaminated with

atrazine were more likely to develop breast cancer compared to women in the area who did

not drink the contaminated water.

The International Journal of Occupational and Environmental Medicine published a study conducted in a Novartis Syngenta factory in St. Gabriel, Louisiana that manufactures

atrazine. The community is 80 percent black. The results concluded that the increase in

prostate cancer in male subjects in the community was concentrated in company employees,

and more prevalent in actively working employees. Further, the prostate cancer increase was

limited to men under 60 years of age.

It is known from five independent laboratories in three different countries that atrazine works by blocking phosphodiesterase, which causes an increase in cyclic AMP (adenosine

monophosphate) and in aromatase activity. The transcription factor SF1 plays an important

role in this process—when SF1 is added to cell lines that do not normally contain it, there is an increase in aromatase activity. When atrazine is added, the increase is even larger.

When breast cancer cells become damaged, they are regulated by aromatase—local

aromatase expression through promoter 2 produces estrogen, which causes cancer cells to

divide. Currently, the number one treatment for breast cancer is an aromatase blocker, which

decreases estrogen and prevents damaged cells from spreading. Novartis, the same company

that produces the aromatase-inducing atrazine, also produces aromatase blockers to treat

breast cancer.

MS. HEATHER LOGAN:

AGRICULTURAL EXPOSURE AND CANCER RISK: AN INNOVATIVE MODEL

FOR PRECAUTIONARY POLICY DEVELOPMENT