Preclinical pharmacologic investigations on a new group of acridine derivatives with oncostatic activity. II. Chronic action.

Influence of 1-nitro-9-(2-dihydroxyethylaminoethylamino)-acridines (C-835) and 1-nitro-9-(3-isopropylamino-propylamino)-acridines (C-846) on animal organs and their basic functions was studied in the chronic action. Rabbits responded to the drugs with considerable tolerance which was less manifested in rats. Slight toxic effect was observed only after maximal doses with which the animals survived 3-month exposure. Enzyme studies and creatinine clearance test did not show any clear-cut impairment of hepatic and renal function. Neither did the preparations influence the red and white blood system, nor the blood clotting time. Microscopic examinations showed their slight (initially) morphologic changes which later passed into degenerative changes (liver, kidney, myocardium) as well as typical of oncostatics, changes in intestinal villi, nuclei and lymphatic system. Also desquamation of intestinal epithelium, hypertrophy of their lamina propria, impairment of spermato- and spermiogenesis as well as atrophy of lymphatic germinal centers and decreased number of small lymphocytes in lymph nodes and spleen were noted. Deviation between the results of function and morphologic tests were discussed. Microscopic changes observed after treatment of the tested acridine derivatives were considered too small to damage the particular organs function.