Archives for posts with tag: Ana Soto

From The DailyMail (quoting Upstream Expert Dr. Ana Soto):

Cancer fears have grown over a chemical widely used in plastic packaging and food-can linings after new research showed that it affected the development of monkey breasts.

Various studies have linked Bisphenol A (BPA) to breast cancer – and now teams at Washington State University and Tufts University have added weight to these findings.

They found that foetal exposure to the plastic additive alters mammary gland development in primates.

Lead author Patricia Hunt said: ‘Previous studies in mice have demonstrated that low doses of BPA alter the developing mammary gland and that these subtle changes increase the risk of cancer in the adult.

‘Some have questioned the relevance of these findings in mice to humans. But finding the same thing in a primate model really hits uncomfortably close to home.’

For the research the structure of newborn mammary glands from BPA-exposed and unexposed female rhesus macaques were compared.

Pregnant monkeys were fed a piece of fruit containing a small amount of BPA each day during the gestational period corresponding to the human third trimester of pregnancy, resulting in blood levels of BPA comparable to those of many humans today.

The researchers found that, at birth, the density of mammary buds was significantly increased in BPA-exposed monkeys, and the overall development of the mammary gland was more advanced compared to unexposed monkeys.

Previous studies have shown that exposing rodents to tiny amounts of BPA can alter mammary gland development, leading to pre-cancerous and cancerous lesions when the animals exposed in utero reach adult age.

The researchers said the primate research makes them confident that the rodent mammary gland is a reliable model to study developmental exposures to chemicals like BPA that disrupt a mammal’s estrogen activity.

Tufts University School of Medicine researcher Ana Soto said: ‘This study buttresses previous findings showing that foetal exposure to low xenoestrogen levels causes developmental alterations that in turn increase the risk of mammary cancer later in life.

‘Because BPA is chemically related to diethylstilbestrol, an estrogen that increased the risk of breast cancer in both rodents and women exposed in the womb, the sum of all these findings strongly suggests that BPA is a breast carcinogen in humans and human exposure to BPA should be curtailed.’

The research appears in the latest Proceedings of the National Academies of Sciences.

More.

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In my interview of Drs. Carlos Sonnenschein and Ana Soto, I asked them about some of their favorite authors and writings on the topic of environmental health.  This video contains their responses, which are also included with links below (duration: 11:34).

Dr. Soto’s Five Favorites:

Dr. Sonnenschein’s Five Favorites:

The full, edited interview is now available on the Upstream Website.

In my recent interview of Drs. Carlos Sonnenschein and Ana Soto, I asked them about how they thought chemicals and the chemical industry should be regulated to better protect human health. Here is the second of two portions of that exchange (duration: 14:27).

Drs. Sonnenschein and Soto respond to the following prompts:

  1. How can a consumer live safely in a toxic environment? 00:40
  2. Can you give me an example of a specific regulation that you would like to see enacted? 03:50
  3. Do we need to change our regulatory mindset in this country? 04:20
  4. What do you mean by the “white paper” approach to regulating chemical?07:50
  5. What is green chemistry? 10:20
  6. What are the impediments to effective regulation, and how is that we overcome them? 11:00

The full, edited interview is now available on the Upstream Website.

In my recent interview of Drs. Carlos Sonnenschein and Ana Soto, I asked them about how they thought chemicals and the chemical industry should be regulated to better protect human health. Here is the first of two portions of that exchange.

Drs. Sonnenschein and Soto respond to the following prompts:

  1. How would you describe the U.S. system of chemical regulation? 00:40
  2. Please describe the “precautionary principle” used in some other countries. 02:10
  3. What is the biggest difference between our regulatory approach and one based on the precautionary principle? 05:50
  4. Why has the U.S. government not caught up with science and employed the precautionary principle? 06:50
  5. What role is the public playing in this issue? 08:10
  6. Are there are any public actors who are making a difference? 10:15
  7. We have made some progress, right? 11:00

The full, edited interview is now available on the Upstream Website.

In my recent interview of Drs. Carlos Sonnenschein and Ana Soto, I asked them about their research on endocrine disruptors. Below is the clip from that portion of the interview.

Drs. Sonnenschein and Soto respond to the following prompts:

  1. What are endocrine disruptors and what effects do they have? 00:40
  2. Are all endocrine disruptors estrogenic? 02:20
  3. How do you determine if a compound is an endocrine disruptor? 03:30
  4. How did scientists first discover the endocrine-disrupting effects of synthetic estrogens? 04:10
  5. Describe the research on endocrine disruptors since then? 05:30
  6. Can you say more about the DES experience and the lessons learned from it? 07:10
  7. What might experiments on rodents teach us about the risks of endocrine disruptors for humans? 010:30
  8. What other risks have scientists attributed to BPA? 12:30

The full, edited interview is now available on the Upstream Website.

In my recent interview of Drs. Carlos Sonnenschein and Ana Soto, I asked them about Bisphenol A (BPA). Below is the clip from that portion of the interview.

Drs. Sonnenschein and Soto respond to the following prompts:

  1. Describe why you changed your focus to BPA. 00:40
  2. What was the original purpose of BPA? 03:15
  3. Where do humans come into contact with these BPA-laden plastics? 04:30
  4. Do you think the public fully appreciates the magnitude of this problem? 06:35

In their responses, they discuss how they discovered several estrogenic chemicals and why BPA became the primary focus of their research in the 1990s.  They explain the origins of BPA, including the fact that it was originally synthesized to be an estrogen, though it was ultimately used in the synthesis of plastics.  They also describe the ubiquity of BPA in our products — including in plastic water bottles, dispersants in inks, and sealants in teeth.

The full, edited interview is now available on the Upstream Website.

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I recently interviewed Drs. Carlos Sonnenschein and Ana Soto.

This video contains the introduction to that interview, in which they responded to the following prompts:

  1. Describe your work before you began studying environmental toxins. 00:00:40
  2. What caused you to shift the focus of your research? 00:02:35
  3. Please say more about the unexpected results in your lab and how you responded.00:04:25
  4. Without the manufacturer’s assistance, how did you discover what the contaminant was? 00:06:25
  5. What is the contaminant, and how is it used? 00:07:55

Through their responses, Drs. Sonnenschein and Soto tell the fascinating story of how a laboratory accident caused them to stop their research and pursue a new project that would eventually reveal to them how plastic tubes were producing estrogenic activity and set them down a new research path.  They also describe how they came to realize that the “problem [of estrogenic activity] was probably much more serious” than they first suspected.

The full, edited interview is now available on the Upstream Website.

With the official launch of the Upstream website scheduled to occur next week, for the next couple of weeks, I will be posting stories and quotations about and by the experts in my first interview: Drs. Carlos Sonnenschein and Ana Soto.

Here are excerpts from an article, titled “Ground-breaking Research Leads to New Cancer Theory,” from Environmental Factor, by Brian Chorley (published May, 2010).

* * *

Carlos Sonnenschein, M.D., and Ana Soto, M.D., have dedicated the majority of their research careers to describing the signals that mediate cellular proliferation. On April 20, the researchers presented their findings during a seminar at NIEHS on investigations of chemicals that mimic the biological actions of estrogen. Their talk, “Carcinogenesis: Development Gone Awry,” also presented evidence from their experiments that lend support to a new theory of carcinogenesis.

The current scientific consensus is that cancer-causing agents result in the uncontrolled proliferation of a single cell. Because this paradigm cannot explain all tumors, Soto and Sonnenschein have developed an alternative theory to describe these not-so-uncommon exceptions.

The tissue organization field theory of carcinogenesis

The prevailing sporadic carcinogenesis theory, known as the somatic mutation theory, explains that carcinogens mutate cells that are normally in a non-growing, quiescent state. These mutations lead to a cascade of programmatic errors that cause a state of irreversible proliferation. Therefore a change in a single cell can lead to tumor formation.

Sonnenschein, drawing on the connection between carcinogenesis and tissue development, explained why  this scenario may not always be the case. “Development is not a program,” he said. “Development decisions are made instead by an ad hoc committee.”

In his tissue organization field theory of carcinogenesis, Sonnenschein characterizes cancer as a disease of the tissue organ. Cells, he explained, are in a default state of proliferation and motility — constantly maintaining homeostasis of the tissue through cellular communication and organization. Disruption of this organization can lead to disease states, such as cancer, as carcinogens target whole tissues, not just individual cells.

Sonnenschein’s theory may account for some situations that somatic mutation theory fails to explain. For example, some cancers are not autonomous — that is, the cancerous cells do not control their own fate. Uncontrolled cellular proliferation, therefore, may be signals from the surrounding milieu, not just simply errors in the cell’s replication machinery.

Bisphenol A alters mammary tissue organization

To support this theory, Soto focused on the team’s mammary development studies in rodents exposed to the xenoestrogen, bisphenol A (BPA).

Pre-natal exposure to BPA, a common component of plastics, alters normal mammary gland development in these models. Soto’s findings demonstrated that in mice BPA accelerates mammary maturation by increasing epithelial cell branching, reorganizing connective tissue, and altering fat deposits. In rats, a common animal model for breast cancer, BPA caused pre-cancerous lesions in the mammary tissue.

These lesions were directly linked to tissue disorganization caused by the BPA exposure during gestation and lactation.

The mechanisms are still unclear

While altered mammary development due to BPA exposure led to abnormal cellular proliferation in these rodent models, the cellular signaling mechanisms involved are still being teased out.

Soto described multiple experiments in progress. One exciting finding was that the methylome — the methylation patterns of the genome — changed constantly with BPA exposure. Soto explained that thousands of methylation sites were altered, but these changes were inconsistent over different points of time during and after the BPA exposure. The challenge is to determine if these methylation changes are causative or simply consequences of the tissue disorganization.

Parallel gene expression analysis may solve part of the mechanistic mystery. Soto believes the preliminary results are encouraging. “The molecular results are consistent with the [mammary] histology… the locale and time of [BPA] exposure is of the essence,” she explained.

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