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Updated: May 16, 2026
Changes in Mammary Gland Morphology and Breast Cancer Risk in Rats
Published on: October 16, 2010
Role of melatonin and luzindole in rat mammary cancer
Ugurlu M Umit1, Terzioglu Berna, Kaya Handan
1Department of General Surgery, School of Medicine, Marmara University, Istanbul, Turkey. umitugurlu@gmail.com
Background:
Recent studies have analyzed the efficacy of various agents in experimental chemoprevention trials. In our study, the effects of melatonin (Mel) and its antagonist Luzindole (Luz) on Heme oxygenase-1 (HO-1) in a NMU (N-methyl-N-nitrosourea)-induced rat mammary carcinoma model are investigated. We aim to demonstrate the relationship between Mel and HO-1.
Methods:
Spraque-Dawley rats were treated with NMU at age 55 days to induce mammary carcinoma. Forty-eight rats were divided into four groups consisting of: (a) physiological saline group (PSG); (b) control group, NMU is given; (c) Mel group (500 μg daily); (d) Mel antagonist Luz group (0.25 mg/kg/day i.p.). The animals were sacrificed; their serum and tissues were sampled for histopathologic evaluation, markers of endocrine derangement (serum prolactin, estradiol, and progesterone levels), apoptotic changes, DNA fragmentation, markers of oxidative stress and HO-1 immune expression were measured.
Results:
Most tumors developed in the Luz group (42%), followed by the control group (33%), and the Mel group (17%). The tumor latency was longer in Mel-treated group (control and Luz at week 17, Mel at week 21). The maximum tumor volume was also smaller in Mel group when compared to control and Luz groups (p < .05). In Mel group estradiol, progesterone, and prolactin levels were decreased compared to control group (p < .001; p < .01; and p < .01) and levels of apoptotic activity and DNA fragmentation ratio increased.
Conclusions:
The increment of HO-1 expression with Mel is described; possible underlying mechanisms of these effects await further investigations.
Insights
Melatonin treatment reduced mammary carcinoma development in rats by decreasing tumor incidence and volume. This suggests melatonin's potential as a chemopreventive agent, possibly through its effects on Heme oxygenase-1.
Area of Science:
- Oncology
- Endocrinology
- Biochemistry
Background:
- Investigating chemoprevention strategies for mammary carcinoma.
- Examining the role of melatonin (Mel) and its antagonist Luzindole (Luz) in a N-methyl-N-nitrosourea (NMU)-induced rat mammary carcinoma model.
- Exploring the relationship between melatonin and Heme oxygenase-1 (HO-1) expression.
Purpose of the Study:
- To investigate the effects of melatonin and Luzindole on mammary carcinoma development in rats.
- To determine the impact of melatonin on hormonal levels, apoptosis, DNA fragmentation, oxidative stress, and HO-1 expression.
- To elucidate the potential chemopreventive role of melatonin.
Main Methods:
- Induction of mammary carcinoma in Sprague-Dawley rats using NMU.
- Treatment of rats with physiological saline, NMU alone, melatonin (500 μg daily), or Luzindole (0.25 mg/kg/day).
- Assessment of tumor incidence, latency, volume, serum hormone levels (prolactin, estradiol, progesterone), apoptotic activity, DNA fragmentation, oxidative stress markers, and HO-1 immune expression.
Main Results:
- Melatonin treatment significantly reduced tumor incidence (17%) and volume compared to control (33%) and Luzindole (42%) groups.
- Melatonin administration increased tumor latency and elevated levels of apoptotic activity and DNA fragmentation.
- Melatonin decreased serum levels of estradiol, progesterone, and prolactin.
Conclusions:
- Melatonin exhibits chemopreventive effects against NMU-induced mammary carcinoma in rats.
- Melatonin's mechanism may involve hormonal modulation, increased apoptosis, and DNA fragmentation.
- An increase in HO-1 expression was observed with melatonin, warranting further investigation into its role.
