Affiliation:
1. Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka, Japan
2. Department of Oral Pathology, Osaka University Graduate School of Dentistry, Osaka, Japan
Abstract
Summary
Objective
The aim of this study was to investigate the toxic effect of cyclophosphamide (CPA) in the development of rodent molars.
Methods
CPA was administered intraperitoneally in postnatal mice between Day 1 and Day 10, and the morphological phenotype was evaluated at Day 26 using micro-computed tomography and histological analysis, including cell proliferation and cell death analyses.
Results
M3 molars of the mice who received 100 mg/kg CPA treatment at Day 6 or M2 molars who received treatment at Day 1 resulted in tooth agenesis or marked hypoplasia. Histological observation demonstrated that CPA treatment at Day 6 resulted in shrinkage of the M3 tooth germs, with a significant reduction in the proliferation of apoptotic cells. Conversely, CPA exposure at Day 2, which occurs at around the bud stage of M3, resulted in crown and root hypoplasia, with reduced numbers of cusp and root. In addition, CPA exposure at Day 10, which is the late bell stage of M3, induced root shortening; however, it did not affect crown morphogenesis.
Limitations
The timing of CPA administration is limited to after birth. Therefore, its effect during the early stages of M1 and M2 could not be investigated.
Conclusion
Defective phenotypes were evident in both crown and roots due to the effect of CPA. Interestingly, the severity of the phenotypes was associated with the developmental stages of the tooth germs at the time of CPA administration. The cap/early bell stage is the most susceptive timing for tooth agenesis, whereas the late bell stage is predominantly affected in terms of root formation by CPA administration.
Funder
Japan Society for the Promotion of Science
Publisher
Oxford University Press (OUP)
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献