Simultaneous assay by six methods of the effect on haemopoietic precursor cells of adriamycin, methyl CCNU, 60Co γ-rays, vinblastine, and cytosine arabinoside

The spleen colony assay, three agar colony assays and two repopulating assays have been employed to measure the effect of single doses of adriamycin, methyl CCNU, 60Co γ-rays, vinblastine and repeated injection of cytosine arabinoside on early haemopoietic precursors. The results show that there is no consistent correlation between the effect of these agents on the six assays, and the differences in proliferation rate of the cells contributing to the various assays could not be demonstrated by the phase specific agents vinblastine and cytosine arabinoside. The relatively high survival of granulocyte repopulating ability after adriamycin and methyl CCNU indicates that the capacity for differentiation and maturation can be influenced by cytotoxic agents so that colony assays while estimating the number of progenitor cells surviving do not necessarily provide a reliable guide to the capacity of the cells for restoring haemopoiesis. Comparison of colony formation by normal bone marrow cells with the three agar colony assay showed that the agar diffusion chamber method gave three times as many colonies and a much smaller variation between experiments compared to the in vitro agar assay with endotoxin mouse serum as colony stimulating factor. The thin layer feeder cell method gave an intermediate number of colonies. (author)