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Further Studies of the Action of a Partially Purified Bacteriocin against a Murine Fibrosarcoma¹

Ontario Cancer Institute [R. P. H.] and Departments of Medical Biophysics [R. P. H.] and Microbiology [H. F-H.], University of Toronto, Toronto, Ontario, Canada M5S 1A8

We have reported previously that a partially purified bacteriocin (PPB) from Escherichia coli HSC₁₀ is toxic to KHT cells growing in vivo as micrometastases but apparently has no activity against a tumor growing i.m. We report here experiments to investigate possible reasons for this difference. The PPB was shown to become less effective against micrometastases, initiated by i.v. injection of KHT cells, as the time between cell injection and PPB treatment increased. The kinetics of the loss of efficacy did not, however, correlate exactly with the growth kinetics of the nodules as assessed by survival following radiation treatment at different times after cell injection. This suggests the possibility of a diffusion limitation although it was found that s.c. injections of PPB were nearly as effective against micrometastases as i.p. injections. We also demonstrated that the lifetime of the majority of the toxic activity of PPB in vivo was relatively short (<1 day) and that the majority of its effect was not caused by stimulating macrophages to act against the tumor cells. The PPB was found to be cytotoxic to KHT cells in vitro but the effect was reduced at high cell density (10⁶ cells/ml). The PPB did not induce an immune reaction against itself in C3H mice nor was it toxic to either bone marrow stem cells or jejunal crypt cells at doses which were effective against KHT micrometastases. We conclude that PPB may have potential as a cytotoxic agent to act against circulating tumor cells or very small deposits of tumor cells but is limited in its efficacy against larger tumor masses probably because of diffusiona and/or cell density effects.

¹ Supported by the National Cancer Institute of Canada, the Ontario Cancer Treatment and Research Foundation, and the University Research Incentive Fund of the Ontario Ministry of Colleges and Universities.

² To whom requests for reprints should be addressed, at Research Division, Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Canada M4X 1K9.

Received 5/ 7/90. Accepted 12/10/90.