Further Studies on the Homograft Response in BALB/c Mice With L1210 Leukemia and a Resistant Subline

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Abstract
Leukemia L1210 and an ascitic subline M46G, carried in DBA/2J mice, and the antifolic-resistant subline C82R, carried in CDBA [(BALB/cAn × DBA/2J)F1] hybrids, were transplanted into homologous BALB/c mice. These transplanted leukemias grew and regressed (homograft response) when inoculum levels of approximately 1 percent leukemic spleen were used. With further dilutions of the inoculum, the proportion of tumor takes terminating in death of the animals was increased markedly. This phenomenon of increased lethality associated with low concentrations of leukemic inoculum was referred to as the “dilution effect.” With antifolic therapy of animals bearing the resistant subline, the homograft response was abrogated, since within a wide range of inoculum concentrations, the animals died. The dilution effect was, in essence, restored when the metabolite citrovorum factor was given simultaneously with amethopterin. Concomitant injection of normal tissue (CDBA spleen and DBA/2J blood) or X-irradiated DBA/2J leukemic spleen prevented the lethality observed with low concentrations of leukemic inoculum. Under these conditions the homograft reaction occurred and the dilution effect was absent.