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      Comparison of biochemical and biological effects of four nitrosoureas with differing carbamoylating activities.

      Cancer research

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          Abstract

          Four chloroethylnitrosoureas with differing degrees of carbamoylating activity were compared for their effects on incorporation of radioactive precursors into macromolecules. The comparisons were made with concentrations that, for each drug, produced a defined biological effect, either an 0.5-log or a 2-log reduction in cloning efficiency from a 1-hr drug exposure. Dose-dependent inhibition of incorporation of labeled precursors into nucleic acids and proteins was observed during the 1-hr drug exposure with either of the two strongly carbamoylating nitrosoureas, 1-3-bis(2-chloroethyl)-u-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; the most extensive inhibition involved incorporation into DNA. No inhibitions were observed during exposure to a weakly carbamoylating nitrosourea (chlorozotocin) or during exposure to 1-(2-chloroethyl)-1-nitrosourea, a compound the carbamoylating activity of which is not agreed upon. By 4 hr after removal of 1-3-bis(2-chloroethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea from the extracellular medium, the cells had partially recovered from the earlier inhibition of radioactive thymidine incorporation. This recovery was, however, dependent upon an undefined factor present in serum. The inhibitions that were observed during the 1-hr drug exposure are clearly not essential to the cytotoxic effect of chloroethylnitrosoureas since no inhibitions occurred with two of the four compounds studied.

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          Author and article information

          Journal
          Cancer Res.
          Cancer research
          0008-5472
          0008-5472
          Aug 1978
          : 38
          : 8
          Article
          149589
          c49c3504-e685-456b-9577-05f32086f0f0
          History

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