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In Vitro

, Volume 16, Issue 8, pp 661–668 | Cite as

Differences between rat liver epithelial cells and fibroblast cells in sensitivity to 8-azaguanine

  • Jules J. Berman
  • Charles Tong
  • Gary M. Williams
Article

Summary

Epithelial and fibroblast cells from adult rat liver were found to differ markedly in their sensitivities to the toxic effects of the purine analog, 8-azaguanine. Epithelial cells were rapidly killed by 8-azaguanine, whereas fibroblast cells suffered no observable toxicity.

The resistance of fibroblast cells was not due to impermeability since it was shown by autoradiography that both cell types took up and utilized exogenous purines. Moreover, both cell types were sensitive to 6-thioguanine. The fibroblast cells, however, possessed a greater guanase activity than did the epithelial cells, measured by conversion of 8-azaguanine to 8-azaxanthine in the cell lines. Both cell types possessed hypoxanthine-guanine phosphoribosyl transferase for phosphoribosylating exogenous purines and thus making them metabolically available. Epithelial cell lysates convert 8-azaguanine to 8-azaguanosine-5′-monophosphate, the toxic metabolite of 8-azaguanine. Fibroblast cell lysates converted much more 8-azaguanine to 8-azaguanosine, an inactive metabolite, than did the epithelial cells. This conversion was presumably due to the much greater activity of 5′-nucleotidase in fibroblasts than epithelial cells; it degrades 8-azaguanosine-5′-monophosphate to 8-azaguanosine.

These differences in purine metabolism suggest that fibroblast resistance to 8-azaguanine is due to the combination of a significant guanase activity that limits the amount of 8-azaguanine available and a high 5′-nucleotidase activity that would result in conversion of 8-azaguanosine-5-monophosphate, the toxic metabolite of 8-azaguanine, to 8-azaguanosine.

Key words

purine metabolism liver cell fibroblast 8-azaguanine 

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Copyright information

© Tissue Culture Association 1980

Authors and Affiliations

  • Jules J. Berman
    • 1
  • Charles Tong
    • 2
  • Gary M. Williams
    • 2
  1. 1.Laboratory of Experimental PathologyNational Cancer InstituteBethesda
  2. 2.The Naylor Dana Institute for Disease PreventionAmerican Health FoundationValhalla

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