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Published on: July 6, 2019
Lobucavir-induced proliferative changes in mice.
Jochen Woicke1, Stephen K Durham, Mark G Mense
1Department of Pathology, Bristol-Myers Squibb Co., P.O. Box 4755, Syracuse, NY 13221-4755, USA. jochen.woicke@bms.com
Summary
This study investigated the carcinogenic potential of lobucavir, a nucleoside analogue. Long-term administration of lobucavir was found to cause various neoplasms in mice, similar to other nucleoside analogues.
Area of Science:
- Toxicology
- Oncology
- Pharmacology
Background:
- Nucleoside analogues are vital in treating viral infections like HIV, CMV, and herpes.
- However, these drugs exhibit toxicities such as anemia, neutropenia, and neuropathy, limiting their use.
- Some nucleoside analogues have demonstrated carcinogenic potential in rodent studies.
Purpose of the Study:
- To evaluate the carcinogenic potential of lobucavir, a nucleoside analogue.
- To compare the tumor spectrum induced by lobucavir with that of other nucleoside analogues.
Main Methods:
- Lobucavir was administered orally to male and female mice at varying doses for 104 weeks.
- Control groups of mice received no lobucavir.
- Neoplasms were identified and characterized using light microscopy.
Main Results:
- Lobucavir induced upper digestive tract squamous cell neoplasia in both male and female mice.
- Female mice also developed cervical, vaginal, and cutaneous squamous cell neoplasia.
- Male mice exhibited Harderian gland adenomas and adenocarcinomas.
Conclusions:
- Long-term administration of lobucavir induces neoplasia in mice.
- The observed tumor spectrum is comparable to that seen with zidovudine and ganciclovir.
