Sensitivity of DBLA-6 leukemia of rats to known antitumor agents in relation to their clinical effects.

Abstract

Of 4 lines of myelogenous rat leukemias induced by N-nitrosobutylurea (NBU), DBLA-6 was selected as a screening model for antileukemic agents because of the following characteristics: a) High transplantability either by intravenous (i.v.) or intraperitoneal (i.p.) inoculation; b) linear relationship between inoculum size and survival time; c) marked increase of leucocyte counts in the peripheral blood as the tumor progresses after intravenous inoculation. To investigate reliability in its predicting clinical efficacy, its sensitivity to known antileukemics was studied. To determine the effects, a change of leucocyte counts in the peripheral blood together with the prolongation of life span was checked in the following systems; i.v.-i.v. (i.v.-inoculation, i.v.-injection), i.v.-i.p., i.p.-i.p., i.p.-i.v. Fifty percent cure was obtained with Vincristine, Vinblastine, Daunorubicin, 6-Mercaptopurine, and alkylating agent 838D or 864T. The success of treatment was measured by decrease of leucocytes. Methotrexate, cytosine arabinoside (Ara-C), and cyclophosphamide showed only poor effects, and Mitomycin C, L-asparaginase, and Bleomycin were ineffective. In addition, the chemotherapeutic effects of Vincristine and 864 on this leukemia were quite dependend both on the route of drug injection and on the site of tumor inoculation. Subsequently, our studies are being extended to cover the correlation between drug distribution and tumor localization or dissemination.