Two S-ethylene substituted phosphoramides were reported by Buckley et al. ( l ) , Burchenal et a L ( 2 ) and Lewis et d ( 3 ) to be as effectii-e as Triethylene melamine in retarding the qrowth of a number of experimental tumors. The inhibitory effect of a large series of ethylenimine derivatives against a wide tumor spectrum has been reported independently by this laboratory(4,S).The purpose of the studies reported here was to select ethylenimine derivatives* which markedlj-.inhibit the metastasizing tendency of the mammary adenocarcinoma of the Hooded Brown Rat.Jlatrrials nrtd methods. Approximately 2 x 2 in111 iragments of mammary adenocarcinoma. R2126, were implanted aseptically by trocar into the subcutaneous tissue of the right side oi inbred Hooded rats weighing 100-120 g. The rats were weighed, housed individually and arranged ' 7 feiiiales and 8 males per group. Treatnients were started 48 hours after implantat ion. Included in each experiment were one saline-treated group that served as a negative control, and one Triethylene-melamine-treated group that served as a positive control. -\ synthetic diet(3) and water were * Supplied by Calco Chemical Division. -4merican Cyanamid Co., Bound Brook, S. J .given ad libitum. The compounds were prepared in buffered saline and the concentrations used as indicated in Table I. Injections were administered intraperitoneally daily or every other day in a volume of 0.5-1.0 ml. The period of treatment was approximately 42 days. At the end of this time all animals were sacrificed and the lungs excised. Observations were made on the gross metastatic lesions of the lungs and a section+ was fixed for histological study. The inhibitory effects on the primary tumor have been reported previously ( 5 ) .Results. The pooled results of several experiments in Table I indicate that the 5 compounds at the levels tested markedly reduce the incidence of metastases to the lungs. Fig. 1 illustrates the effect of these compounds on the gross metastatic tumors of the lung. The control lungs on the left show the typical metastatic growths. On the right is shown typical treated lungs with no visible metastatic lesions. Histologically the control lungs show tumor masses so extensive that the normal architecture of the lungs has been nearly destroyed. The lungs of the treated animals t The authors are indebted to Mrs. Hester S. Sch,urr for the preparation of the tissues for hktological study.
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