Dr. John F. Dicello’s objective is to determine whether non-toxic drugs can reduce the risk of cancers arising from low-dose environmental exposures. His group is determining the risk of cancers resulting from exposures to galactic and solar radiations. They are collaborating with Dr. David Huso’s group who is determining whether specific types of drugs can be used after exposure to reduce the risks of these diseases. By observing rodents exposed to radiations similar to those in space, they examine the types and frequencies of tumors as well as damage to the pituitary and other tissues as a function of particle type (radiation quality) and dose.
Overview
In Vivo Carcinogenesis Studies with the Sprague-Dawley Rat
Principal Investigator:
John F. Dicello, Ph.D.
Organization:
Johns Hopkins University School of Medicine
Technical Summary
The risks of cancer to personnel in space from the naturally occurring radiations are generally considered to be one of the most serious biomedical limitations associated with long-term human space missions, as noted in two recent reports of the National Research Council/National Academy of Sciences. The paramount goals of the Radiation Effects Team for the National Space Biomedical Research Institute are to determine carcinogenic consequences of radiations in space in an appropriate model, to develop effective physical and pharmaceutical countermeasures, and to study ways to reduce the risks of cancer and other diseases associated with such exposures.
During interplanetary missions, personnel in space will be exposed to galactic cosmic rays, including high-energy protons and energetic ions. (Ions with high energy (E) and atomic numbers (Z) greater than one are usually called HZE particles.) In addition, solar events will produce radiation fields of high intensity for short but irregular durations. The level of intensity of these radiations is considerably higher than that on Earth's surface, and the biological risks for carcinogenesis to astronauts are consequently elevated. Our group is examining the risk of cancers in model systems resulting from their low-dose exposures to photons, protons and iron by using ground-based accelerators, which are capable of producing beams of such particles at energies comparable to those encountered in space. We have successfully conducted a series of experiments using a 1-GeV iron beam at the Brookhaven National Laboratory and 250-MeV protons at Loma Linda University Medical Center's proton synchrotron facility. As part of these studies, we have been collaborating with a companion project (David Huso, Principal Investigator) that is investigating the potential for anti-estrogen-based pharmaceuticals to reduce the risk of cancer after irradiation at the level of doses and for particle types expected in space. The hypothesis is that carcinogenesis in in vivo models can be used to extrapolate that the risk in humans and the risk of hormone-stimulated cancers such as breast cancer can be reduced by the subsequent administration of appropriate drugs after exposures to protons and densely ionizing radiations such as energetic heavy ions and neutrons. Additionally, the hypothesis is that the precursors of cancer can be altered at the promotion and progression stages of the diseases rather than the initiation. If this latter hypothesis is correct, it could reduce or eliminate the need for administering drugs in anticipation of significant exposures.
Theoretical studies carried out in a collaboration between scientists at NASA-Johnson Space Center and Johns Hopkins University are providing methods and predictions that are being used to assess the levels of radiation risks to be encountered, and to evaluate appropriate strategies for countermeasures. Continued collection and analysis of data from this project over the next three years will further enhance the precision of our estimates of biologic response and reduce the large uncertainties associated with previous assessments of risks for activities in space.
The research has consisted of four successive series beginning with a feasibility study to develop the logistics and infrastructure for these types of studies and followed by three studies to investigate the incidence of mammary carcinomas and the change in risk with the subsequent administration of Tamoxifen. The final three studies are still in progress, but the first one has been successfully completed and the data are being examined and analyzed. The initial results provide some of the first in vivo data for the risk of cancer from both energetic protons and heavy ions. Initial results from the companion project indicate validation of the hypothesis that the risk can be reduced by subsequent pharmaceutical intervention with drugs.
Although the work in this project is primarily directed toward risks associated with space travel, the problem of protracted exposures to low-levels of radiation is one of national interest in our energy, defense and homeland security programs, and the present results suggest new paradigms for addressing such risks.
This project's funding ended in 2005