PMID: 3756862Oct 1, 1986Paper

Cross-sensitivity of methylating agents, hydroxyurea, and methotrexate in human tumor cells of the Mer- phenotype

Cancer Research
K R Maynard, P G Parsons

Abstract

Five human tumor cell lines of the Mer- phenotype sensitive to killing by the methylating agent 5-(3-methyl-1-triazeno)imidazole-4-carboxamide were sensitive to hydroxyurea (HU) compared with 15 cell lines resistant to methylating agents (Mer+ phenotype). In a study using fewer cell lines, Mer- cells were also sensitive to methotrexate but not to seven other agents including the antimetabolites 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil. Cells sensitive to HU were designated the Hu- phenotype. Five autologous Mer+ lines, derived in vitro by treating Mer- lines with methylating agents, did not become resistant to HU or methotrexate (Mer+ Hu- phenotype). All Mer+ lines studied had enhanced ability to reactive methylated adenovirus. Adenovirus was inactivated by prolonged treatment with HU, but no enhanced reactivation of HU-treated virus was found in Mer+ cell lines. Cell survival after 5-(3-methyl-1-triazeno)imidazole-4-carboxamide treatment was not significantly decreased by HU, nor was replication of methylated adenovirus inhibited by HU in Mer- or Mer+ lines. Replication of untreated adenovirus was poor in Mer- cells treated with HU, indicating that sensitivity of cells to HU was associated with inhibition of DNA sy...Continue Reading

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