Development of Resistance to Folic Acid Antagonists in a Transplantable Lymphoid Leukemia

Summary

A development of resistance has been shown in 3 separate sublines of a transplantable lymphoid leukemia, L1210, in strain dba mice following successive transplants in mice treated with the MTD of 3 different PGA antagonists: 4-amino-N¹⁰ methyl PGA, 4-amino-9, N¹⁰ dimethyl PGA and 4-amino-9 methyl PGA. All 3 sublines continue to be resistant in subsequent transplant generations following emergence of resistance. Subline AD-resistant leukemic cells grown in mice not given the folic acid antagonist for 7 successive transplant generations continue to be resistant to 4-amino-9, N¹⁰ dimethyl PGA. Resistance developed to one of these antivitamins was found not to be independent of resistance to the others. AM-resistant leukemic cells were found to grow better in animals receiving the MTD of 4-amino-N¹⁰ methyl PGA than in animals untreated with this antivitamin or given PGA parenterally.