The two compounds, 4-(p-dimethylaminostyryl)-quinoline and 4-(^-diethylaminostyryl)quinoline, which possessed the greatest anti-lymphoma properties, are not soluble in water and only slightly soluble in prop-ylene glycol. Among the compounds which we synthesized, two (the mono- and the di-hydrochloride of 4-(p-diethylaminostyryl)quinoline) were soluble in aqueous solution. The dihydrochloride, being the more soluble, was selected for this study.
The sixteen rats in our experimental series varied in weight from 150 to 200 gm. Each rat was injected intraperitoneally with 1 ml. of lymphogenous blood (from the heart) of a rat in which lymphoma 8 had been implanted subcutaneously fourteen to eighteen days previously. The number of white cells present in blood of normal rats is more variable than that of humans. Counts range from 6,000 to 18,000, with an average of 9,000 per c.mm. ; the majority (60-70 per cent) of the white blood cells are lymphocytes rather than polymorphonuclear neutrophils. As shown in Fig. 1, the white cells in the blood increased slowly during the first five to seven days after transmission of the disease ; the number then rose rapidly, reaching as high as 115,000 per c.mm. twelve days after the intraperitoneal injection. Stained preparations (Wright's stain) of the blood of untreated rats showed numerous large lymphoblast-like cells, some in mitotic division. On the twelfth day all the rats were extremely ill. On this day, twelve of the rats were each given a single intravenous injection of 4 mgm. of 4-(p-diethylaminostyryl)quinoline dihydrochloride dissolved in J ml. of sterile distilled water. The remaining four rats were not treated. On the following day the four untreated and one treated rat were dead. On the second day after treatment, the surviving eleven rats had recovered their vigour, and the white blood cells had dropped to 8,500-10,000 per c.mm. (Fig. 1). On the third day after treatment, the white blood cells were 7,500-9,500 per c.mm. The rats gained weight and the white blood cells remained at this level during the following fourteen days (Fig. 1). In stained blood smears during this period, only normal white cells could be found. The large lymphoblasts present in the blood before treatment seemed to have disappeared entirely.Fig. 1. Total white blood-cell counts in rat lymphocytic leukaemia 8 before and after intravenous administration of 4-(p-di ethyl - aminostyryl)quinoline dihydrochloride. Normal range, hatched ; average, stippled
These results seem to indicate that the intravenous administration of 4 mgm. of 4-(p-diethylaminostyryl)-quinoline dihydrochloride was followed by a remission of the leukgamic blood picture in rat lymphocytic leuksemia 8, but not by a depression of the total white count below the normal level in a fourteen-day observation period.This investigation was supported in part by grants from the Pew Memorial Foundation and the Medical Research Foundation and in part by grant (7-285((77) from the National Cancer Institute, Department of Health, Education and Welfare.