Tumorigenesis in Immunosuppressed Sprague-Dawley Rats: A Case Study of Exposures to NMU Carcinogen and MCF-7 Cancer Cell Lines

Abstract

Breast cancer is a leading cause of morbidity and mortality worldwide. Reliable in vivo models are essential for studying tumor pathogenesis and therapeutic interventions. This study evaluated breast tumor induction in Sprague Dawley (SD) rats using either MCF-7 cancer cell lines or N-methyl-N-nitrosourea (NMU). Female SD rats were divided into three groups: one received 50 mg/kg NMU, another was injected with 0.1 mL containing 10⁵ MCF-7 cells, and a third served as untreated control. All groups were immunosuppressed with ketoconazole and cyclosporine. Body weight and breast tissue palpation were monitored for 8 weeks. Hematological indices were assessed before and after immunosuppression. Finally, the rats were humanely sacrificed, harvested organs and breast tissues were examined histologically. Immunosuppression caused a significant reduction in neutrophils and lymphocytes (p < 0.05). Progressive weight loss was observed in the NMU and MCF-7 treated groups. Palpable breast tumors appeared after 6 weeks in NMU-exposed rats, with histology confirming malignant lesions and comedo necrosis. NMU also induced hemorrhages in the lungs and spleen, and hyperchromasia in cardiac and renal tissues, indicating systemic toxicity. No tumors were detected in MCF-7 treated rats within the same period, and organ damage was minimal. In conclusion, NMU at 50mg/kg successfully induced breast tumors in SD rats within 6 weeks but also caused notable toxicity in non-target organs. These findings highlight the need for strategies to minimize systemic damage when developing in vivo breast cancer models.