Effect of retained components of excised tumor upon coexisting tumor

Abstract

Effects of locally treated and retained tumor tissue on the growth of a tumor at another site were investigated using Lewis rats bearing syngeneic fibrosarcoma. When an established tumor had completely regressed upon repeated intratumoral injections of l-phenylalanine mustard (PhM), the growth of secondarily transplanted tumor cells was inhibited. However, early excision of the PhM-injected tumor prevented the development of this effect. To study this effect directly, we excised one of the two established tumors in each thigh, and reinoculated into the excision wound either freeze-lysed 1 × 10 8 tumor cells (TC) or lysate chemically modified with PhM (PTC). We found that TC inoculation into the excision wound in 7 rats inhibited the growth of the remaining tumor and extended survival time (mean ± SE, 27 ± 1 days). With inoculation of PTC into the excision wound, the remaining tumor regressed and survival was significantly prolonged (32 ± 2 days). In contrast, 7 untreated rats, each bearing two tumors, had a mean survival time of 22 ± 0.1 days. Excision of one tumor (6 rats) did not affect the growth of the remaining tumor or survival time (23 ± 1 days). We employed PhM to modify the immunogenicity of TC. However, if PhM dissociates from PTC, its cytotoxic effect may directly inhibit growth of the distant tumor. To examine this possibility, we divided 30 rats who had excision of one tumor, into three groups of 10. They were given PhM (1.75 mg/rat) sc injection (Group 1), intrawound TC inoculation plus PhM sc injection (Group 2), or intrawound inoculation of TC mixed with 1.75 mg of PhM (Group 3). The animals in Group 2 produced a greater inhibition of the remaining tumor than the animals Group 1. Group 3 showed a significant regression of the distant tumor and survival time averaged 7 days longer than that in Group 1. Thus, the aforementioned possibility is unlikely. Repeated study also confirmed the effect of TC inoculation. These results strongly suggest that the retention of oncolysate, especially the PhM-modified lysate, in the tumor excision wound is beneficial to the development of resistance against remote tumor.