Preclinical toxicology studies with acyclovir: genetic toxicity tests

Area of Science:

• Toxicology and Pharmacology
• Genetics and Mutagenesis

Background:

• Acyclovir (ACV) is a key antiviral medication for herpes infections.
• Evaluating the mutagenic and carcinogenic potential of ACV is crucial for patient safety.

Purpose of the Study:

• To assess the mutagenic and carcinogenic potential of Acyclovir (ACV).
• To evaluate ACV's effects across a range of in vitro and in vivo assays.

Main Methods:

• Conducted a battery of in vitro assays including Ames Salmonella, E. coli DNA repair, yeast gene conversion, and mammalian cell gene mutation/cytogenetics.
• Performed in vivo assays such as the mouse dominant lethal assay and rodent bone marrow cytogenetics.
• Utilized metabolic activation systems in select in vitro tests.

Main Results:

• Negative results were observed in most in vitro and all in vivo assays at maximum tolerated doses.
• Positive mutagenic effects (chromosomal damage) were noted in vitro at high ACV concentrations or prolonged exposure.
• An unusual clastogenic effect was observed in Chinese hamsters at 5 times the maximum tolerated dose.

Conclusions:

• Acyclovir (ACV) demonstrates potential as a chromosomal mutagen in vitro under specific high-dose or long-exposure conditions.
• The in vivo data and lack of single-gene mutations suggest limited genotoxic risk at therapeutic levels.
• Further investigation into the human genetic risk associated with ACV is warranted.