[ RadSafe ] Calabrese reviews major NCI drug test database, shows hormesis, as normal biology

[Muckerheide]

Friends,

Re the medical applications in the last paragraph, low-dose radiation immune
function stimulation:  Was shown to prevent and treat cancer, and applied
for infections and inflammatory conditions, from the 1910s to the late-40s
and beyond. (It is still applied today for specific conditions.)

It was displaced by wonder drugs (serum drug profits in the 1930s, by FDA).
This was reestablished after WWII by suppressing Manhattan Project data and
research.  NCI was a major controller since the late-40s.

Regards, Jim Muckerheide
==================

Date: January 3, 2007

Measuring The Effects Of Very Low Doses: New Study Challenges How Regulators
Determine Risk

Science Daily ‹ A new study of a large U.S. National Cancer Institute
database provides the strongest evidence yet that a key portion of the
traditional dose-response model used in drug testing and risk assessment for
toxins is wrong when it comes to measuring the effects of very low doses,
says Edward J. Calabrese, a scientist at the University of Massachusetts
Amherst. The findings, based on a review of more than 56,000 tests in 13
strains of yeast using 2,200 drugs, are published in the journal
Toxicological Sciences and offer strong backing for the theory of hormesis,
Calabrese and his colleagues contend.

Calabrese says the size of the new study and the preponderance of evidence
supporting hormesis, a dose-response phenomenon in which low doses have the
opposite effect of high doses, is a breakthrough that should help scientists
assess and predict risks from new drugs, toxicants and possibly carcinogens.
Calabrese says, "This is a fundamental biological principle that has been
missed."

Calabrese says that the field of toxicology got the dose response wrong in
the 1930s and this mistake has infiltrated all regulations for low-dose
exposures for toxic chemicals and drugs. These low-dose effects can be
beneficial or harmful, something that the regulations miss because they are
currently based on high-dose testing schemes that differ greatly from the
conditions of human exposures.

In this latest study, which uses data from a large and highly standardized
National Cancer Institute tumor-drug screening database, Calabrese says the
evidence of hormesis is overwhelming. In the study, high doses of anticancer
drugs frequently inhibit yeast growth, but at low doses they enhance growth,
exactly what the hormesis model predicts.

Whether one accepts the hormesis theory is not the critical public policy
issue, according to Calabrese. He says that the major issue is that the risk
assessments models used by the federal Environmental Protection Agency and
the Food and Drug Administration fail to accurately predict responses in the
low-dose zone, that is, where people live most of their daily lives.

Calabrese also says challenging the existing dose-response model has
profound public policy and health implications. "I believe the hormesis
model is the fundamental dose-response and government testing and risk
assessment procedures should reflect that," Calabrese says. For example, in
environmental regulations, it has been assumed that most carcinogens possess
real or theoretical risks at low levels, and therefore must be nearly
completely removed from the environments to assure public safety. Some would
contend that if hormesis is the correct model for very low levels, that
cleanup standards may have to be significantly changed. Others, however, see
the evidence as insufficient for such radical change and worry about other
factors that can influence the effects of chemicals in low doses. The new
study promises to add fuel to the debate, Calabrese says.

Calabrese also suggests that the findings may have important implications
for the pharmaceutical industry and medical practices. He says that hormesis
is likely to identify new life-saving drugs that were missed through
traditional testing and to markedly improve the accuracy of patient dosing,
which will not only improve health outcomes but also reduce adverse side
effects.

Note: This story has been adapted from a news release issued by University
Of Massachusetts Amherst.