The purpose of this study was to create a model of recurrent tongue cancer after cryosurgery for cancer experimentally induced by 4NQO in rats, to investigate the proliferative activity of residual cancer cells, and to evaluate the antitumor effect of peplomycin. The proliferative activity of residual cancer cells the and vascular architecture of recurrent tumor were examined in rats given peplomycin and in those not given peplomycin. Recurrent tumor was macroscopically detected 8 weeks after cryosurgery. Residual cancer cells were observed in the submucosa in all cases. These findings suggested that radical cure cannot be achieved by cryosurgery according to lesion size. A high mitotic index was seen from 4 weeks after cryosurgery, and a high labeling index was noted after 8 weeks, suggesting that re-proliferation of cancer cells that have high proliferative activity is promoted by the formation of new blood vessels and the recovery of blood flow. Re-proliferated cancer cells invaded existing blood vessels, suggesting that they had a high grade of malignancy. Administration of peplomycin immediately after cryosurgery suppressed tumor cell proliferation after 4 weeks but not after 8 weeks. Residual cancer cells were found in both deep and peripheral regions, although the proliferation of these cells wsa suppressed. Destruction of blood vessels was not detected in rate given peplomycin after 4 weeks indicating that peplomycin inhibited the destruction of blood vessels by cancer cells. The architecture of regenerated blood vessels in rats given peplomycin differed from that in rats not given peplomycin. The results suggested that the effect of chemotherapy against by residual cancer cells is reinforced by newly formed vessels and increased vascular permeability.
