| Summary: | Weinberg and Emerman (1989) demonstrated that differential housing conditions
alter the growth of the transplantable androgen-responsive Shionogi mouse mammary
carcinoma (SC115). In addition it was shown that changes in the immune system are
influenced both by housing and the presence or absence of tumour. The objective of this
thesis was to determine if the immune system and, more specifically, if natural killer
(NK) cells may be involved in mediating the effects of differential housing on SC115
tumour growth.
In a preliminary study in our laboratory, T lymphocyte proliferation in the spleens
of mice in different housing conditions was measured. The initial study of this thesis was
designed to replicate these experiments in order to obtain sufficient data for statistical
analysis. At the time of tumour-cell injection, mice raised individually from the time of
weaning either remained individually housed (II) or were placed in groups of 5 (IG);
mice raised in sibling groups of 3 from the time of weaning either remained in their
rearing groups (GG) or were separated and housed individually (GI). Three wk after
tumour-cell injection, spleens were removed and cells were cultured with or without the
mitogen Concanavalin A (Con A) to stimulate proliferation of T lymphocytes. This
proliferation was measured by [³H] - thymidine incorporation. In the absence of Con A,
there were no differences in spleen cell growth among animals from the 4 housing groups, whether or not they were injected with tumour cells. With Con A stimulation,
lymphocyte proliferation was decreased in IG mice. However, changes in response were
eliminated in animals injected with tumour cells.
The major studies of this thesis focused on the investigation of the role of NK cell
activity in modulating tumour growth rate in our model. NK cell lytic activity is
modulated by both the presence of a tumour and psychosocial stressors. Further, it has
been shown that the immune system responds within days to stressors. In this thesis, NK
cell activity at early time points following formation of experimental groups and tumourcell
or vehicle injection was examined. First, a protocol to measure splenic NK cell
cytolytic activity in our mice was established. Using this protocol, NK cell activity was
examined 3 d and 1 wk following tumour-cell or vehicle injection and rehousing.
Following vehicle injection, groups did not differ significantly in NK cell activity. All
vehicle injected groups were significantly lower in NK cell activity than tumour-cell
injected groups and there was no significant change in NK cell activity from 3 d to 1 wk.
Significant stimulation of splenic NK cell activity occurred 3 d post-injection of SC115
cells. However, no correlation was observed between the level of splenic NK cell
activity and tumour growth rate induced by the housing condition. It was concluded that
either splenic NK cell activity does not accurately reflect NK cell activity at the tumour
site or that NK cells are not a significant regulator of the differential tumour growth rates
seen in this model.
|
|---|
