| Description |
The mechanisms of natural resistance to neoplastic disease are unknown. The hypothesis has been established that in a system involving white mice (albino Mus musculus) and Ehrlich ascites tumor (EAT) a mechanism of normal resistance exists against the establishment of the neoplasm. The concept of natural resistance to establishment of neoplasia in the models employed is derived from experiments yielding dose-response relationships; that is, reproducible LD50 values can be determined by different routes of challenge with counted numbers of viable cells. The LD50 values differed markedly among the intraperitoneal (ip), subcutaneous (sc), and intravenous (iv) routes indicating differences in the degree of resistance by these routes. Furthermore, the degree of resistance could be significantly increased by iv immunization with a sublethal dose of viable tumor cells. An avenue of approach that deserves exploration is the potential role of cellular defenses in such natural resistance. Although much work has been done with respect to humoral defenses, relatively few data exist concerning cellular defenses and neoplastic diseases. The role played in living cells in the induction of increased resistance was investigated. By Whole body x-irradiation at varying intervals of time after iv injection with EAT cells did not result in increased incidence of lung tumors in mice. The experimental results obtained did not support the hypothesis that dormant tumor cells mediate some mechanism by which living cells induce increased resistance to subsequent tumor challenge. Indirect evidence for the existence of cellular defenses in natural resistance was exhibited by x-irradiated animals. Whole body x-irradiation (300 r, LD0) of normal mice 4 days prior to ip or sc challenge with EAT cells resulted in depressed resistance compared to nonirradiated animals. Irradiation of immunized mice, to the same extent as normals, did not depress resistance to challenge with EAT cell, indicating the role of humoral defenses in induced resistance. There was no evidence of agglutination, phagocytosis or tumor cell destruction in the peritoneal fluid from either immune or normal animals. In contrast, macrophages from immunized animals adhered to EAT cells when incubated in vitro at 37? C. This effect could not be demonstrated with S-37 tumor cells. Rabbit antibody or guinea pig complement significantly reduced tumor cell viability when incubated in vitro prior to ip inoculation into normal mice. Under similar condition rabbit antibody plus complement completely neutralized EAT cells. Neither homologous serum nor lysates of macrophages demonstrated any capacity to neutralize EAT cells. No difference in mortality ratios were observed in mice challenged ip with a mixture of normal or immune mouse peritoneal macrophages and EAT cells. The ratio employed was 4 macrophages to 1 tumor cell and the time incubation prior to challenge was 2.5 and 5 hours. Macrophages from immunized or normal mice incubated with tumor cells in the ratio 1200 macrophages to 1 tumor cell and subsequently injected into normal mice showed an increase in survival time over animals receiving EAT cells alone. No difference was noted, however, between the effects of normal and immune macrophages. Immune lymph cells extended the survival time of mice receiving a mixture of lymph node cell and EAT cells via the sc route. This effect could not be demonstrated via the ip route. Ehrlich ascites tumor cells were injected ip or sc into mice acclimatized to low ambient temperatures following challenge. The viability of EAT cells was not affected, and acclimatized mice showed significant delays in mortality compared to the control animals kept at room temperature; however, the final mortalities were similar in the acclimatized and room temperature exposed mice. Mice kept at low temperature and challenged with S-37 tumor cells showed a significant difference in the mortality and survival time with challenged via the sc route. |
