The focus of the invited presentations was on the issue of the toxicologi
cal implications of biological adaptations. The selection of topics and
speakers was designed to consider critically the concept of hormesis, not
only in a broad, conceptual manner (Chapter 1, “Hypotheses on Mamma
lian Aging, Toxicity, and Longevity Hormesis: Explication by a Generalized
Compertz Function,” Harold Boxenbaum), but also at molecular and bio
chemical levels (Chapter 2, “The Role of the ‘Stress Protein Response’ in
Hormesis,” Joan Smith-Sonneborn); (Chapter 3, “DNA Repair: As Influ
enced by Age, Nutrition, and Exposure to Toxic Substances,” Ron Hart et
al.); (Chapter 4, “Biochemical Mechanisms of Biphasic Dose-Response
Relationships: Role of Hormesis,” Harihara M. Mehendale). These three
mechanistically oriented presentations offered a complementary perspective
on the diverse range of molecular mechanisms that can become activated at
low levels of toxicant exposure and lead to organismal responses seen in the
presentation of Boxenbaum.
Although the major focus of the meeting dealt with responses to low
levels of chemical exposures, it should be noted that considerable research
has been directed toward the effects of low levels of radiation on biological
systems. In fact, in 1987 the journal Health Physics published a 1985 con
ference proceedings on the topic of radiation hormesis. Consequently,
Robert Anderson provided a synthesis of current research on this topic in
his presentation “Effects of Low-Dose Radiation on the Immune Response”
(Chapter 5). Emmanuel Farber (Chapter 6, “Cellular Adaptation as an
Important Response During Chemical Carcinogenesis”) offered a unifying
perspective on how the liver adapts to genetic insults via the formation of
hepatocytes that are resistant to subsequent toxic insults due to a diminished
capacity to bioactivate xenobiotics and an enhanced capacity to facilitate
xenobiotic excretion. The relationship of the resistant hepatocyte theory
and modern molecular understandings of the process of carcinogenesis was
addressed. It is Farber’s opinion that the early and intermediate stages in
carcinogenesis, as embodied in the resistant hepatocyte, are principally
“physiological-adaptive,” and are distinguishable from the progressive
stages of carcinogenesis involving frank malignancy.
The final presentation was devoted to biostatistical considerations when
designing studies that address issues associated with the biological responses
to low doses of chemicals and radiation, as well as issues in the interpreta
tion of the findings from such studies (Chapter 7, “Biostatistical
Approaches for Modeling U-Shaped Dose-Response Curves and Study
Design Consideration in Assessing the Biological Effects of Low Doses,”
Tom Downs).
This workshop provided an important benchmark for future BELLE
activities. The presentations have indicated that biological systems have an
impressive array of adaptations that are turned on in response to various
stresses, including physiological stress, as well as exposure to radiation,
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