Archives for the month of: August, 2010

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.

Advertisements


Download the entire Upstream Pamphlet here (pdf).



Executive Summary

The 33-year old law that was supposed to ensure that Americans know what chemicals are in use around them, and what health and safety hazards they might pose, has produced a regulatory black hole, a place where information goes in – but much never comes out. The reason is that under the 1976 Toxic Substances Control Act (TSCA), the chemical industry has been allowed to stamp a “trade secret” claim on the identity of two-thirds of all chemicals introduced to the market in the last 27 years, according to an Environmental Working Group (EWG) analysis of data obtained from the Environmental Protection Agency (EPA). These include substances used in numerous consumer and children’s products.

EWG’s analysis also showed that:

  • The public has no access to any information about approximately 17,000 of the more than 83,000 chemicals on the master inventory compiled by the EPA.
  • Industry has placed “confidential business information” (CBI) claims on the identity of 13,596 new chemicals produced since 1976 – nearly two-thirds of the 20,403 chemicals added to the list in the past 33 years.
  • Secrecy claims directly threaten human health. Under section 8(e) of TSCA, companies must turn over all data showing that a chemical presents “a substantial risk of injury to health or the environment.” By definition compounds with 8(e) filings are the chemicals of the greatest health concern. In the first eight months of 2009 industry concealed the identity of the chemicals in more than half the studies submitted under 8(e).
  • From 1990 to 2005, the number of confidential chemicals more than quadrupled – from 261 to 1,105 — on the sub-inventory of substances produced or imported in significant amounts (more than 25,000 pounds a year in at least one facility). In July 2009 the EPA released the identity of 530 of these chemicals, lowering the number of these moderate- and highproduction
    volume secret chemicals to 575.
  • At least 10 of the 151 high volume confidential chemicals produced or imported in amounts greater than 300,000 pounds a year are used in products specifically intended for use by children age 14 or younger. TSCA is an extraordinarily ineffective law. Its failings have been repeatedly documented by the Government Accountability Office, Congressional hearings, and independent investigations. But it has generally been assumed that the law required an accurate public inventory of chemicals produced or imported in the United States.

As this investigation shows, it does not.

Instead we have a de-facto witness protection program for chemicals, made possible by a weak law that allows broad confidential business information (CBI) claims, made worse by EPA’s historic deference to business assertions of CBI.

EPA data compiled in response to an EWG information request show that a large number of these secret chemicals are used everyday in consumer products, including artists’ supplies, plastic products, fabrics and apparel, furniture and items intended for use by children. But EPA cannot share specific information on these chemicals even within the agency or with state and local officials.

Industry has a stranglehold on every aspect of information needed to implement even the most basic health protections from chemicals in consumer products and our environment. This must be changed. A chemical’s identify and all related health and safety information must be made available to the public with no exceptions.

* * *

You can download the entire report here.

%d bloggers like this: