Single cell suspensions of two allogeneic tumours (W-256 and Y-P388) injected intravenously produced macrocolonies in the lungs of rats. Colony forming efficiency (CFE, the number of colonies produced by each viable cell injected) was low in 6-week or older rats but was markedly increased by 1000-1500 rad local thoracic irradiation (LTI) given 7-14 days before the tumour cell injection, or by antilymphocytic serum (ALS) but not by sublethal whole body irradiation (WBI). Similarly, LTI increased the incidence of pulmonary metastases produced by a solid tumour growing in the leg muscle. Stimulation of CFE by LTI was a strictly local phenomenon and not due to effects of irradiation on thymus, spleen or other tissues of the rat. LTI failed to increase CFE in immunized rats. It is concluded that (1) LTI stimulates clonogenic growth of tumour cells arrested in the lungs, by causing inflammatory reactions accompanied by regenerative cellular proliferation of lung tissue, which increases the “plating” efficiency of tumour cells, (2) the increase in CFE in lungs is not due to suppression of immunity to tumour growth by LTI. Images Fig. 3

These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.

Summary.-Two rapidly growing allogeneic tumours, sublines of Yoshida (Y-P388) and Walker (W-256) injected intravenously in single cell suspensions produced tumour macrocolonies in the lungs of rats within 7 days. Y-P388 produced similar but fewer colonies in the kidneys. Colony forming efficiency (CFE) in lung was high in weanling rats given either sublethal whole body irradiation (WBI) or a single dose of rabbit anti-rat lymphocytic serum (ALS) to suppress immunity. In immunologically intact weanlings CFE was much lower and many 7-day old colonies showed signs of regression. CFE for primary tumour cell challenges decreased rapidly and markedly with increase in age of host during the first 1-2 weeks after weaning. This resistance to growth of a primary challenge in lungs of older rats was not significantly reduced by WBI but was decreased by ALS. CFE of a secondary challenge of tumour cells injected intravenously in rats which had been previously immunized with heavily irradiated (HR) tumour cells was very low; it was not significantly increased by WBI but was moderately increased by ALS. In weanling rats given lethal (900 ra4) WBI, 1 hour before intravenous injection of tumour cells, treatment with bone marrow (BM) cells derived from normal adult donors increased CFE, whereas BM (or spleen) cells from immunized donors decreased CFE. The results suggest that ALS and WBI not only increase tumour CFE by suppressing immunity to tumour growth but also " condition " host tissue (tumour bed) in such a way as to facilitate the survival, " take " and initial replication of grafted tumour cells before the rats recover from the immunosuppressive effects of these treatments.

Summary.-Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed.

SUMMARY.-The effects of local X-irradiation of a solid, rapidly metastasizing sarcoma in the rat on kinetics of dissemination and growth of metastases in lymph nodes and lungs are described. Corresponding dose-effect curves obtained for growth of the primary tumour (Pr)