Diffusion bioassays are being extensively used for determining the antibiotic potency of drugs and for predicting genotoxicity and carcinogenicity of chemicals. The drug is placed at the center of a petri dish containing a bacterial lawn in an agar gel, and after a certain incubation period, one observes a concentric ring around the center, marking the toxic area. We propose to develop a mathematical model that will enable us to obtain an equation relating the minimal inhibitory concentration c(tox) to the radius of the toxic zone r(tox), so that by performing diffusion experiments (which are fast, efficient and inexpensive) and measuring the size of r(tox), it will be possible to calculate c(tox). This quantity is very important in evaluating the sensitivity of microorganisms to antibiotics and in determining their therapeutic doses. In the case of DNA damaging agents, we would like to use c(tox) as a criterion for their damaging potency. The mathematical model of the assay is given by a two-dimensional diffusion equation describing the changes in drug concentration due to diffusion, decay of the chemical and consumption by bacteria. The equation will be solved numerically with the aid of the computer, and a program will be specifically designed for this purpose. A vast amount of experimental data is already available and will be analyzed through this model.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
5R23CA037820-03
Application #
3446559
Study Section
(SSS)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Awerbuch, T E; Ryder, E F; Faraggi, D (1987) A program which determines mutagenic concentrations of chemical carcinogens via a diffusion bioassay. Comput Methods Programs Biomed 25:31-8
Awerbuch, T E; Lustman, L (1987) A mathematical model for determining minimal inhibitory concentrations (MICs) via diffusion assays. J Theor Biol 129:219-30