A model is described for testing the effect of exposure to subtoxic challenge upon cellular integrity. The model incorporates Physarum polycephalum as a biological assay system, the ability of the cell to traverse the cell cycle as an indicator of cell integrity, and the use of repeated challenge by cadmium ion as a mechanism for amplifying the response to subthreshold exposure. A sensitivity profile of Physarum, developed by periodic exposure to 5 x 10-4 m Cd2+ for 30 min throughout the cell cycle, contains two peaks of sensitivity resulting in mitotic delay, one in early S and the other in late G2. Physarum accommodates to a subtoxic challenge of Cd2+ by developing a protective response: Exposure to 10-4 m Cd2+ for 30 min in early G2 (0.45 cycle), which does not delay mitosis, protects Physarum against a mitotic delay of 105 min resulting from exposure to 4 x 10-4 m Cd2+ for 30 min in late G2 (0.75 cycle). Protection persists for at least two cell cycles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22745/1/0000300.pd