Related Experiment Videos
Ductal carcinoma in situ in rat mammary gland
K A Crist1, B Chaudhuri, S Shivaram
1Department of Surgery, Medical College of Ohio, Toledo 43699-0008.
Abstract:
Antiestrogen therapy has been proposed as a treatment option for ductal carcinoma in situ (DCIS). However, its effectiveness has not been evaluated in the laboratory due to lack of an animal model. The present study was undertaken to evaluate the incidence, time span, and number of mammary glands involved with DCIS in a rat model treated with N-nitroso-N-methylurea (NMU). Sprague Dawley female rats 44 to 49 days old were treated with two iv doses of 5 mg NMU/100 g body wt given 7 days apart, initiated at diestrus. Animals were killed at intervals beginning 21 days following first injection. Breast tissues were evaluated following routine H&E stain. Standard histologic criteria were followed to establish the diagnosis of DCIS. The number of glands involved with DCIS increased from one to seven with time from first injection. This model demonstrates an incidence of 87% for DCIS and 0% for invasive Ca between 22 and 45 days following NMU injection. Nine rats were sacrificed between 50 to 60 days and five showed invasive carcinoma. This model appears suitable for studying the efficacy of hormone or chemoprevention in the progression of DCIS to invasive Ca.
Insights
A new rat model effectively mimics ductal carcinoma in situ (DCIS), showing an 87% incidence. This model is crucial for evaluating antiestrogen therapies and understanding DCIS progression to invasive cancer.
Area of Science:
- Oncology
- Animal Models
- Carcinogenesis
Background:
- Antiestrogen therapy is a potential treatment for ductal carcinoma in situ (DCIS).
- Laboratory evaluation of antiestrogen therapy for DCIS is limited by the absence of a suitable animal model.
- Understanding DCIS progression is vital for developing effective treatments.
Purpose of the Study:
- To develop and validate a rat model for studying ductal carcinoma in situ (DCIS).
- To evaluate the incidence, time course, and mammary gland involvement of NMU-induced DCIS in rats.
- To establish a preclinical model for assessing interventions against DCIS progression.
Main Methods:
- Sprague Dawley female rats (44-49 days old) received two intravenous doses of N-nitroso-N-methylurea (NMU).
- Animals were euthanized at various time points starting 21 days post-injection for histological analysis.
- Mammary tissues were stained with Hematoxylin and Eosin (H&E) to diagnose DCIS and invasive carcinoma.
Main Results:
- The NMU-treated rat model exhibited an 87% incidence of DCIS between 22 and 45 days post-injection.
- The number of DCIS-involved mammary glands increased over time.
- Invasive carcinoma was observed in 5 out of 9 rats sacrificed between 50 and 60 days, indicating progression.
Conclusions:
- This rat model accurately replicates key features of ductal carcinoma in situ (DCIS).
- The model demonstrates a high incidence of DCIS and allows for the study of its progression to invasive cancer.
- This preclinical model is suitable for evaluating the efficacy of hormone therapies and chemopreventive agents against DCIS.