Tumor and marrow damage occurring from methotrexate, monofluoromethotrexate, difluoromethotrexate, and dichloromethotrexate

1961 Cancer Research  
The effects of methotrexate, 3',5'-dichloromethotrexate (DCM), and two new antifolic acid compounds, monofluoromethotrexate (MFM) and difluoromethotrexate (DFM), on the C3H mouse marrow count and a transplanted tumor, the 6C3HED lymphosarcoma, were studied. The data were presented in the following forms: plots of the regression lines of marrow counts and tumor weight responses against dose of compound used; slopes of the regression lines; relative potencies of the bone marrow destruction; and
more » ... titumor activity as compared with methotrexate as a standard. MFM caused the greatest damage to the marrow; DFM was almost equal to methotrexate in its destructive effect on the marrow. DCM caused no detectable destruction of the marrow in a dose range of 6.6 to 38 mg/kg; at a range of 75 to 168 mg/kg mild destruction was detected. All compounds caused suppression of tumor weight with increase in dose. The slopes of the plots of the regression lines of tumor weight against dose were all close to --1.0. The relative potency of the antitumor activity of MFM and DFM and DCM compared with that of methotrexate showed that it took 3, 19, or 99 times as much compound, respectively, to cause the same amount of tumor suppression as resulted from methotrexate (dose range, .198-~.~5). The marrow destructive effect required 1.7, 31, or ~00 times as much MFM, DFM, or DCM as methotrexate, respectively. DCM, 33 mg/kg/day for 54 days or a total dose of 178~ mg/kg, did not cause depression of the marrow, white, red, or peripheral blood differential counts.
pmid:13781792 fatcat:i6hbc2hjhvfqzo3lie55z6n7c4