Developmental defects in rats treated postnatally with 5‐lododeoxyuridine (IUDR)

Abstract

Sprague-Dawley rats were treated sc with 100-400 mg/kg/day 5-iododeoxyuridine (IUDR) for 5 days beginning at 1, 5, or 10 days of age. Hair and somatic growth were markedly reduced in rats given 400 mk/kg beginning at 1 day of age. Animals were examined histologically at 10 or 20 days of age. Cerebellar cortical lesions were evident after the highest dosage in animals killed at 10 days of age, but lesions were of lesser magnitude in all series killed at 20 days of age. Retinal dysplasia was observed in rats treated beginning at 1 day of age. Lesions were characterized by thinning of the retina, undulations, and rosette formation in outer retinal layers. Foci of renal dysplasia were evident in rats treated beginning at 1 day of age. Poorly differentiated glomeruli and tubules together with nests of primordial epithelial cells, indicative of impaired nephrogenesis, were located in the superficial cortex. It is known that developmental defects can occur in the cerebellum, retina, and kidney of animals infected perinatally with certain cytolytic viruses. However, these appear to be the first studies demonstrating that a halogenated uridine given to newborn animals may result in obvious renal cortical and retinal dysplasia.

Comparison of the Antiviral Effects of 5-Methoxymethyl-deoxyuridine with 5-Iododeoxyuridine, Cytosine Arabinoside, and Adenine Arabinoside

“…Organs with rapidly dividing cells such as the gastrointestinal tract, bone marrow, the fetus, and lymphoid tissue (4,13,18,19,25) are the usual sites where toxicity is manifest. Our data suggest that the antiviral effects of MMUdR are selectively directed against virus replication and not due to a drastic alteration of the physiological state of host cells.…”

“…5-Iodo-2'-deoxyuridine (IUdR) (21), 9-f3-n-arabinofuranosyladenine (Ara-A) (6,16), and 1-f3-n-arabinofuranosylcytosine (Ara-C) (25) have been found to be effective to varying degrees in the treatment of infections due to herpesviruses. However, their high toxicity (9,13,25), especially to rapidly proliferating cells (18,19), limits the usefulness of these nucleoside analogues in the treatment of viral infections. Recently, another nucleoside derivative, 5-methoxymethyl-2'-deoxyuridine (MMUdR), was synthesized (3), and in preliminary experiments it showed antiviral activity against infectious bovine rhinotracheitis virus (14).…”

Effects of Adenine Arabinoside on Cellular Immune Mechanisms in Humans

“…Gastrointestinal and central nervous system toxicity also limit the usefulness of some of the potential antiviral compounds. Ara-C and idoxuridine have both been shown to inhibit cerebellar development in fetal and young animals, causing serious concern in recommending their use in neonatal deoxyribonucleic acid viral disease (5). Minor but irritating side effects such as oral mucosal ulceration and alopecia are unfortunately common.…”

Effect of anti-herpesvirus drugs on human and bovine lymphoid function in vitro

“…Usually narrow limits exist between the concentration of drug that is virostatic or virocidal and the concentration that causes cellular injury. Because antiviral agents are usually directed at either nucleic acid synthesis or protein synthesis, organs and tissues undergoing rapid proliferation, such as the gastrointestinal tract, hair follicles, bone marrow, the fetus, and the stimulated lymphoid tissues, are sites where toxicity is usually apparent (4,7,9,14,17,18,24,25).…”

“…However, almost all agents available to date have undesirable side effects, since they also have adverse effects on normal cell metabolism. This effect is especially apparent in rapidly dividing tissues, such as the gastrointestinal tract, hair follicles, bone marrow, and lymphoid tissues (4,7,9,14,17,18,24,25). In using anti-herpesvirus compounds it is important that they should not affect the immune response, especially cellular immunity, since this component of the immune response is assumed to be important for recovery from herpesvirus infections (1,2,16,22).…”