METABOLIC COMPETITION STUDIES OF 2'-FLUORO-5-IODO-1-BETA-D-ARABINOFURANOSYLCYTOSINE IN VERO CELLS AND HERPES-SIMPLEX TYPE-1-INFECTED VERO CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 26  (3) , 587-593
Abstract
2''-Fluoro-5-iodo-1-.beta.-D-arabinofuranosylcytosine (FIAC) is a potent antiviral agent with minimal cytotoxicity. In Vero cells, incorporation of labeled dCyd and dThd into the acid-insoluble DNA fraction was, respectively, competitively and noncompetitively inhibited by FIAC. In herpes simplex type 1 (HSV-1) infected Vero cells, these inhibition patterns became noncompetitive. The inhibition constants of FIAC on dThd and dCyd incorporation into the acid-insoluble fraction during a 15-min period were greater than 30 .mu.M which were much higher than the antiviral concentration of FIAC (ED90 = 0.003-0.013 .mu.M) for continuous exposure. Incorporation of dUrd into acid-insoluble DNA was inhibited by 10 .mu.M FIAC in HSV-1-infected Vero cells, but not in uninfected cells. The radioactivity of [2-14C]FIAC was incorporated into the acid-insoluble DNA fraction, and this incorporation in uninfected cells was strongly inhibited by 10 .mu.M dCyd but not by dThd. The incorporation in HSV-1-infected Vero cells was strongly inhibited by 10 .mu.M dThd but not by dCyd. Evidently, FIAC behaves metabolically like dThd, dUrd or 5-iodo-dUrd in HSV-1-infected cells but like dCyd in noninfected cells. Combined use of dCyd and FIAC may reduce cytotoxcity of FIAC or incorporation of FIAC into host cell DNA without affecting its antiviral activity. This finding is of significance since, for practical reasons, incorporation of FIAC into host cell DNA needs to be reduced as much as possible.

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