Cell Culture Studies on Antiviral Agents: I. Action of Cytosine Arabinoside and Some Comparisons with 5-Iodo-2-Deoxyuridine.

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Abstract
Summary Cytosine arabinoside (CA) was shown to have antiviral activity in cell culture against the DNA viruses of herpes simplex, B-virus, pseudorabies, vaccinia, swine pox and fowl pox, but inactive against several adenoviruses and RNA viruses. Comparative tests were run with 5-iodo-2-deoxvuridine (IUDR) and CA. Cytotoxicity in vitro was more marked with CA. Newly planted cells showed toxicity at 0.5 to 1 γ/ml of CA, contrasted to 12.5 to 50 γ/ml of IUDR. In established monolayers, CA toxicity was not acute below 100 γ/ml and IUDR below 1000 γ/ml. Comparative antiviral potency of CA and IUDR against herpes virus in vitro fluid cultures showed CA to be much more active; however, in agar using plaque suppression, both chemicals gave identical endpoints. A single passage of herpes simplex virus in the presence of 500 γ/ml of IUDR resulted in a virus culture resistant to IUDR. The virus after 10 passages in the presence of 500 γ/ml of IUDR was found to have a similar titer in the presence or absence of IUDR. The 6th IUDR free passage of the 10th IUDR passed virus reached similar titers in the presence or absence of IUDR. Herpes simplex virus growth in CA occurred only at low drug levels. Virus populations unaffected by 1000 γ/ml of IUDR were sensitive to 10 γ/ml of CA. A combination of 100 γ/ml of IUDR and 10 γ/ml of CA completely inhibited virus growth, ergo, no resistant virus. Minuscule amounts of CA or IUDR could be detected in whole blood, serum or extracts of several tissues by the plaque suppression method. Concentrations of 0.2 γ/ml could be detected in human serum containing a high titer of herpes simplex antibodies if the serum was first precipitated with warm acetone.

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