Quantitative determination of half-lifetimes and mutagenic concentrations of chemical carcinogens using a diffusion...

It is possible to deduce quantitative information about the mutagenic concentrations of direct carcinogens and procarcinogens from the well-known experiment in which a droplet of a chemical is put at the center of a petri dish containing a bacterial lawn in an agar gel. The model employed relates the mutagenic action to the space-time concentration profile of the diffusing substances. The range of mutagenic concentrations, in particular the lower limit Cmut, at which mutations occur, can be calculated from knowledge of the radii of the mutagenic zone. The only parameters necessary for the calculation of Cmut are the diffusion coefficient, D, which can be calculated, and the half-lifetime of the mutagenic substance, tau 1/2, which can be obtained from the diffusion experiments. The system was tested with N-methyl-N'-nitro-N-nitrosoguanidine (NG), N-methyl-N-nitrosourea (MNU), ethyl methanesulfonate (EMS), and acetoxydimethylnitrosoamine (AcDMN), which are direct carcinogens, and with nitrosomorpholine (NM) and nitrosopyrrolidine (NP), which are procarcinogens. As a consistency check, homogeneous experiments (dose-response curves) at low concentrations of the chemicals were also conducted. However, the statistical analysis of the results showed that the homogeneous assay is not adequate for determining threshold concentrations. Using the concept of the threshold to rank the tested chemicals according to mutagenic potency, the ranking is: NG greater than NP greater than MNU greater than AcDMN greater than EMS.