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Enhancement of natural metastases by nonadherent spleen cells from wide field x-irradiated syngeneic donors
(28)
CONCURRENT AND SUBSEQUENT TUMORS IN THE SAME HOST--A MODEL TO EVALUATE THE HOST TUMOR INTERACTION Oscar A. Mendiondo, Herman D. Suit, and Robert S. Sedlacek
Edwin L. Steele Laboratory for Radiation Biology Department of Radiation Medicine, Massachusetts General Hospital Harvard Medical School, Boston, Mass. Experimental evidence demonstrates an immune rejection reaction (IRR) directed against tumor cells in some animal tumor systems. In the case of FSa, a methylcholanthrene-induced fibrosarcoma of the C3Hf/Sed mouse, the IRR is manifested by a decrease in the TCD50 and an increase in the TD50 in activiely or passively immunized hosts. FSa was transplanted in the right and the left legs of C3Hf/Sed mice and each tumor was given 3750 rad when 8 mm in diameter. That does is the TCD50 for 8 mm FSa growing as one isotransplant In this present experiment the two tumors in any one mouse showed per animal. a strong tendency to respond similarly, e.g. permanent regression or local If one of the two tumors transplanted into each animal were a recurrence. non-immunogenic mammary carcinoma, the distribution of local control and recurrence following irradiation with a TCD50 dose was purely probabilistic with 50% of the animals exhibiting one tumor destroyed and one recurring. Mice previously cured of FSa by radiation showed a stronger tendency to reject a second FSa transplant than mice that previously had a local recurrence needing amputation of the leg for local control. Retransplants are more easily controlled by radiation in the group successfully treated for the first transplant. These data indicate that within an inbred population, some mice have the capacity to react effectively against the tumor challenge and that said capacity is inherent to the host. The implications of these experiments for assessing host response to tumors will be discussed.
(29)
ENHANCEMENT OF NATURAL METASTASES BY NONADHERENT SPLEEN CELLS FROM WIDE FIELD X-IRRADIATED SYNGENEIC DONORS
H. Moroson, Ph.D., M. Schechter, M.S., T. Herskovic, M.D., and I. Kurzman, M.S. Division of Radiobiology, Department of Radiology New York Medical College, New York, N.Y. 10029
Other workers have shown that sublethal whole body x-irradiation (WBI) of mice creates conditions favoring tumor cell growth uncorrelated with host immunocompetence (Hewitt and Blake, Br. J. Cancer 3&, 23, 1977; Peters, Br. J. Cancer 31, 293, 1975). We confirmed that WBI of normal W/Fu rats prior to inoculation 5th ME/H carcinoma cells (previously shown to be nonimmunogenic by usual excision-challenge methods) leads to enhanced (two-fold) growth of metastases (p=O.O06)
89
In addition it was found that nonadherent syngeneic spleen cells from x-irradiated normal honors mixed with ME/H carcinoma cells (ratio of effector:tumor cells = 2OO:l) when inoculated i.m. into syngeneic rats in a Winn test significantly enhanced growth of natural metastases and primary tumor (~(0.01). Enhancement of primary tumor resulted with the 13762 mammary adenocarcinoma in Fischer rats (p(O.004). The tumor enhancing effect was lost if spleen cells were disrupted prior to mixing with tumor cells. Spleen cells from non-irradiated rats had no influence on growth of ME/H tumor but slightly enhanced 13762 tumor (p
(30)
IMMUNOLOGICAL RESPONSES TO TWO DIFFERENT MODELS OF MICROMETASTASES OF A MOUSE TUMOR R.M. SutherlandI,
E.M. Lord2, J. Landryl, M. Baird3, and 11. Siemann3
DEPARTMENTS OF RADIATION BIOLOGY AND BIOPHYSICS1, RADIATION 0NCOLOGY3, MICROBIOLOGY2, CANCER CENTER, UNIVERSITY OF ROCHESTER, NEW YORK 14642 The formation and growth of micrometastases may be affected by a variety We investigated the of host factors including immunological reactions. ability of host lymphoid cells to infiltrate and modify the growth and survival of EMT6 mammary sarcoma cells using two different models of micrometastases - artificial lung nodules and multicellular spheroids in vivo. Micrometastases in lung were produced by i.v. injection of tumor cells into syngeneic Balb/cKa mice. Multicellular spheroids of 600-800 urn diameter were grown in vitro and injected into the peritoneum of sensitized or nonCell suspensions were prepared sensitized syngeneic or allogeneic mice. from lungs or spheroids recovered at different times after injection. Infiltrating host cells were quantified and characterized morphologically and There was significant infiltration by lymphocytes and macrofunctionally.
90
CONCURRENT AND SUBSEQUENT TUMORS IN THE SAME HOST--A MODEL TO EVALUATE THE HOST TUMOR INTERACTION Oscar A. Mendiondo, Herman D. Suit, and Robert S. Sedlacek
Edwin L. Steele Laboratory for Radiation Biology Department of Radiation Medicine, Massachusetts General Hospital Harvard Medical School, Boston, Mass. Experimental evidence demonstrates an immune rejection reaction (IRR) directed against tumor cells in some animal tumor systems. In the case of FSa, a methylcholanthrene-induced fibrosarcoma of the C3Hf/Sed mouse, the IRR is manifested by a decrease in the TCD50 and an increase in the TD50 in activiely or passively immunized hosts. FSa was transplanted in the right and the left legs of C3Hf/Sed mice and each tumor was given 3750 rad when 8 mm in diameter. That does is the TCD50 for 8 mm FSa growing as one isotransplant In this present experiment the two tumors in any one mouse showed per animal. a strong tendency to respond similarly, e.g. permanent regression or local If one of the two tumors transplanted into each animal were a recurrence. non-immunogenic mammary carcinoma, the distribution of local control and recurrence following irradiation with a TCD50 dose was purely probabilistic with 50% of the animals exhibiting one tumor destroyed and one recurring. Mice previously cured of FSa by radiation showed a stronger tendency to reject a second FSa transplant than mice that previously had a local recurrence needing amputation of the leg for local control. Retransplants are more easily controlled by radiation in the group successfully treated for the first transplant. These data indicate that within an inbred population, some mice have the capacity to react effectively against the tumor challenge and that said capacity is inherent to the host. The implications of these experiments for assessing host response to tumors will be discussed.
(29)
ENHANCEMENT OF NATURAL METASTASES BY NONADHERENT SPLEEN CELLS FROM WIDE FIELD X-IRRADIATED SYNGENEIC DONORS
H. Moroson, Ph.D., M. Schechter, M.S., T. Herskovic, M.D., and I. Kurzman, M.S. Division of Radiobiology, Department of Radiology New York Medical College, New York, N.Y. 10029
Other workers have shown that sublethal whole body x-irradiation (WBI) of mice creates conditions favoring tumor cell growth uncorrelated with host immunocompetence (Hewitt and Blake, Br. J. Cancer 3&, 23, 1977; Peters, Br. J. Cancer 31, 293, 1975). We confirmed that WBI of normal W/Fu rats prior to inoculation 5th ME/H carcinoma cells (previously shown to be nonimmunogenic by usual excision-challenge methods) leads to enhanced (two-fold) growth of metastases (p=O.O06)
89
In addition it was found that nonadherent syngeneic spleen cells from x-irradiated normal honors mixed with ME/H carcinoma cells (ratio of effector:tumor cells = 2OO:l) when inoculated i.m. into syngeneic rats in a Winn test significantly enhanced growth of natural metastases and primary tumor (~(0.01). Enhancement of primary tumor resulted with the 13762 mammary adenocarcinoma in Fischer rats (p(O.004). The tumor enhancing effect was lost if spleen cells were disrupted prior to mixing with tumor cells. Spleen cells from non-irradiated rats had no influence on growth of ME/H tumor but slightly enhanced 13762 tumor (p
(30)
IMMUNOLOGICAL RESPONSES TO TWO DIFFERENT MODELS OF MICROMETASTASES OF A MOUSE TUMOR R.M. SutherlandI,
E.M. Lord2, J. Landryl, M. Baird3, and 11. Siemann3
DEPARTMENTS OF RADIATION BIOLOGY AND BIOPHYSICS1, RADIATION 0NCOLOGY3, MICROBIOLOGY2, CANCER CENTER, UNIVERSITY OF ROCHESTER, NEW YORK 14642 The formation and growth of micrometastases may be affected by a variety We investigated the of host factors including immunological reactions. ability of host lymphoid cells to infiltrate and modify the growth and survival of EMT6 mammary sarcoma cells using two different models of micrometastases - artificial lung nodules and multicellular spheroids in vivo. Micrometastases in lung were produced by i.v. injection of tumor cells into syngeneic Balb/cKa mice. Multicellular spheroids of 600-800 urn diameter were grown in vitro and injected into the peritoneum of sensitized or nonCell suspensions were prepared sensitized syngeneic or allogeneic mice. from lungs or spheroids recovered at different times after injection. Infiltrating host cells were quantified and characterized morphologically and There was significant infiltration by lymphocytes and macrofunctionally.
90