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 petri dish containing a bacterial lawn in an agar gel, and after a certain incubation period, one observes concentric rings around the center, marking the toxic and mutagenic zones. A mathematical model that enables to obtain an equation relating the minimal inhibitory concentration c/tox to the radius of toxic zone rtox was developed: so that by performing diffusion experiments (which are fast, efficient and inexpensive) and measuring the size of r/tox, it is possible to calculate c/tox. Similarly a relationship was obtained between the minimal mutagenic concentration c/mut and the size of the mutagenic zone r/mut. c/tox is very important in evaluating the sensitivity of microorganisms to antibiotics and in determining their therapeutic doses. In the case of DNA- damaging agents, c/tox could be used as a criterion for their damaging potency. The sensitivity of the models to the various parameters included in the equations will be investigated. This will be done via an appropriate program that computes c/mut and a simulation program that determines c/tox. For the purpose of verifying the model the vast amount of experimental data that is already available will be compiled and used to calculate c/tox. The procedure for determining c/tox will be developed into a """"""""userfriendly"""""""" interactive program, thus making it available for routine use in clinical settings and in laboratories engaged in screening for potential carcinogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037820-04
Application #
3175669
Study Section
(SSS)
Project Start
1987-07-15
Project End
1990-06-30
Budget Start
1987-07-15
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
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