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By Bobby Scott, Ph.D.
Lovelace Respiratory Research Institute
Albuquerque, NM
This presentation will focus on mathematical models we have
developed for characterizing radiation-induced neoplastic
transformation of aneuploid C3H 10 T1/2 cells by low-LET X
and gamma rays or high-LET alpha and neutron irradiations
(in vitro). The focus of the research is on integrating
dosimetry (including microdosimetic), molecular (e.g.,
genomic damage induction, repair/misrepair, mutations),
and cellular effects information (e.g., neoplastic
transformation, cell killing). Our models lead to rather
complicated analytical solutions that are difficult to
reviewuate (parameter estimation problem) using conventional
regression methods. We have had some success with the Bayesian
inference approach however. Our Bayesian analyses are
implemented via what is called Markov chain Monte Carlo
(MCMC) methods. We are using BUGS software (windows version)
to carry out the MCMC calculations. The MCMC calculations
are very challenging. Associated with this work we have
introduced the area of biological microdosimetry (paper
in press) for low level exposure to ionizing radiation.
Some of the rather complicated math associated with our
modeling of radiation-induced neoplastic transformation
of cells is presented on the web (pdf format) at:
http://www.radiation-scott.org/neotrans1.pdf . Application of our
modeling approach to real data for neoplastic is also
demonstrated on the web (pdf format) at:
http://www.radiation-scott.org/bayesian.pdf . The first
author, H. Schollnberger, is a postdoctoral participant
that has been working with me for over a year now. The
model presented for neoplastic transformation is called
NEOTRANS1 and does not include cell death (modeled indirectly).
A more recent model (NEOTRANS2) includes two modes of cell
death (apoptosis and necrotic death) but only apoptosis is
considered important at very low radiation doses.
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