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Amethopterin Transport in Ehrlich Ascites Carcinoma and L1210 Cells¹

Laboratories of Pharmacology, Children's Cancer Research Foundation, and Department of Pathology and Medicine, Harvard Medical School, Boston, Massachusetts 02115

Accumulation of amethopterin by L1210 and Ehrlich ascites cells in vitro was mediated by a slow, temperature-sensitive, and partly saturable process. The structural specificity of the process could be measured by competition studies; differences were found between the two cell lines. At physiologic drug levels, i.e., those found in vivo during drug therapy, concentrative uptake of amethopterin was found in L1210 but not in Ehrlich cells. This may explain the sensitivity of L1210 to amethopterin and the lack of sensitivity of the Ehrlich cells. A correlation was found between affinity of several amethopterin derivatives for the L1210 transport process and the effectiveness of these compounds in inhibition of tumor growth in vivo.

¹ This investigation was supported by Contract PH-43-66-541 from the Cancer Chemotherapy National Service Center of the National Cancer Institute and by Grant C 6516 from the National Cancer Institute, NIH.

Received 1/25/67. Accepted 5/ 2/67.