A model to study drug effects on lymphoma and normal cell populations using the AKR/J mouse

The existence of an AKR subline, AKR(Rb6.15)1A1d, with a chromosome marker provided a means to differentiate between proliferating lymphoma and normal cell populations within a single animal. An AKR(Rb6.15)1A1d lymphoma cell line has been maintained for 6 yr by serial passage in AKR/J recipients. The mice die in 7 +/- 2.0 days with evidence of extensive infiltration of the tissues by lymphoma cells. Cytogenetic analysis showed that approx. 1% of the metaphase cells in the bone marrow of mice at day 1 of the lymphoma passage were of the AKR(Rb6.15)1A1d donor-type. This increased to 54% by day 4 and 96% by day 6. The number of donor-type metaphase cells per humerus increased from 3.4 +/- 0.29 (X 10(3] at day 1 to 2.0 +/- 0.49 (X 10(5] at day 4 with a concomitant decrease in the number of non-lymphoma host-type metaphase cells. The population doubling time of donor-type metaphase cells per humerus was 12 +/- 1.4 h. At day 4, there was a significant decrease in the percentage of donor-type metaphase cells in mice that had been treated with BCNU (19.0 +/- 5.85%) or spirogermanium (38.6 +/- 5.85%) 24 h earlier. For BCNU treated animals, this also represented a decrease to 4.4 +/- 1.1 (X 10(4] donor-type metaphase cells per humerus.