Decreased tyrosine phosphorylation in tumour cells resistant to FCE 24517 (tallimustine).

Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s).