Some Factors Affecting the Host-Mediated Assay Response

The host-mediated assay was initially conceived as a system for determining the mutagenic potential of mammalian metabolites of foreign compounds for bacteria (1). In practice, a genetically defined indicator microorganism is injected into the peritoneal cavity of mice which are then administered the substance under test, either orally or parenterally. After a specified time usually 3 hr-the mouse is sacrificed and the organisms are recovered; they are then handled by standard bacteriological techniques for determination of the mutant frequency. An increase in the mutation frequency above the solvent control indicates an induction of mutation. In order to further understand the relationship between the host animal's metabolic state and the mutagenic response of the indicator microorganisms, the following study was undertaken. Three compounds were studied: two carcinogenic nitrosamines, dimethylnitrosamine (DMNA) and N-nitrosomorpholine (NM), which need metabolic activation for their mutagenic and carcinogenic activities (1-7) and the nitrosamide N-nitroso-N-methylurea (NMU), which does not require metabolic