Facilitation of nodal metastasis from a non-immunogenic murine carcinoma by previous whole-body irradiation of tumour recipients

Abstract

Of 193 CBA mice kept under prolonged observation after excision of small intradermal transplants of a non-immunogenic tumour (CBA Carcinoma NT), 27 (14%) presented with local recurrence, 19 (10%) with regional lymphnodal metastasis (RNM) and 72 (37%), with pulmonary metastasis +/- other systemic metastases. When mice were exposed to sublethal whole-body irradiation (WBI) before tumour transplantation, the incidence of RNM rose to approximately 80% and the latent period was reduced from approximately 60 days to approximately 40 days after tumour transplantation. This enhancement of RNM by WBI was undiminished when the interval between WBI and tumour transplantation was increased from 1 to 90 days. An explanation for this effect in terms of immunosuppression by the WBI is unlikely for the following reasons: the tumour was non-immunogenic by standard quantitative tests; the effect persisted long after the expected time for recovery of immune reactivity; and i.v. injection of normal marrow and lymphoid cells after WBI failed to reduce the effect. That the effect was systemic was proved by failure of local pre-irradiation of the tumour bed or regional node to enhance RNM. The effect was not observed when WBI was given 4 days after excision of tumours. These and other experiments failed to indicate the mechanism of the effect of WBI, but its long persistence suggests that it may relate to stored lethal radiation damage in migrating cells of slow turnover tissues.