Rapid development of resistance to antifolates in vitro: possible clinical implication.


Within three repeated 7-day incubation periods with either methotrexate (MTX) or trimetrexate (TMTX), human colon adenocarcinoma cells (HCT-8) developed high levels of resistance to these drugs, as evidenced by approximately 20- and 50-fold increases, respectively, in the median effective doses. Similarly, within six short-term exposures (4 hours) to the… (More)