Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats
Abstract
:1. Introduction
2. Results
2.1. Estrogenic Effect of Test Compounds (Short-Term Experiment 1)
2.2. Cell Proliferation in the Mammary Gland (Short-Term Experiment 2)
2.3. Long-Term Study (Experiment 3)
2.3.1. Body, Organ Weights, Food, and Water Consumption
2.3.2. Survival
2.3.3. Histopathological Analysis of Mammary Glands
2.3.4. Histopathological Analysis of Uteri
2.3.5. Blood Hematology and Biochemistry
3. Discussion
4. Experimental Section
4.1. Chemicals
4.2. Test Compounds
4.3. Animals
4.4. Short-Term Experiment 1
4.5. Short-Term Experiment 2
4.6. Long-Term Experiment (Experiment 3)
4.7. BrdU Immunohistochemistry
4.8. Blood Hematology and Biochemistry
4.9. Statistical Analysis
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Treatment | No. Rats a | Fibroadenoma | Fibroma | Adenoma | AdCa | ||||
---|---|---|---|---|---|---|---|---|---|
Mammary Glands | |||||||||
Incidence (No. Rats (%)) | |||||||||
DMBA, ENNG | 21 | 20 (95.2) | 7 (33.3) | 3 (14.3) | 1 (4.8) | ||||
DMBA, ENNG → PM, 0.03% | 20 | 19 (95) | 8 (40) | 2 (10) | 6 (30) | ||||
DMBA, ENNG → PM, 0.3% | 20 | 19 (95) | 8 (40) | 4 (20) | 7 (35) * | ||||
DMBA, ENNG → PM 1% | 21 | 20 (95.2) | 5 (23.8) | 4 (19.1) | 6 (28.6) | ||||
DMBA, ENNG → IA, 0.2% | 21 | 18 (85.7) | 3 (14.3) | 2 (9.5) | 6 (28.6) | ||||
Vehicle | 5 | 1 (20) | 0 | 0 | 0 | ||||
Vehicle → PM, 1% | 6 | 1 (16.7) | 0 | 0 | 0 | ||||
Multiplicity (No./Rat) | |||||||||
DMBA, ENNG | 21 | 10.90 ± 4.93 d | 0.55 ± 0.89 b | 0.15 ± 0.37 | 0.05 ± 0.22 | ||||
DMBA, ENNG → PM, 0.03% | 20 | 9.85 ± 5.39 | 0.40 ± 0.50 | 0.10 ± 0.31 | 0.40 ± 0.68 | ||||
DMBA, ENNG → PM, 0.3% | 20 | 8.30 ± 4.93 | 0.50 ± 0.69 | 0.20 ± 0.41 | 0.45 ± 0.69 # | ||||
DMBA, ENNG → PM 1% | 21 | 7.95 ± 4.26 | 0.29 ± 0.56 | 0.19 ± 0.40 | 0.33 ± 0.58 | ||||
DMBA, ENNG → IA, 0.2% | 21 | 6.90 ± 5.02 * | 0.14 ± 0.36 | 0.10 ± 0.30 | 0.43 ± 0.75 | ||||
Vehicle | 5 | 0.20 ± 0.45 | 0 | 0 | 0 | ||||
Vehicle → PM, 1% | 6 | 0.17 ± 0.41 | 0 | 0 | 0 | ||||
Uterus | Dilatation | Endometrial HPL | AdCa | Polyps | |||||
Mild | Moderate | Severe | Total | S | A | ||||
Incidence (No. Rats (%)) | |||||||||
DMBA, ENNG | 21 | 8 (38.1) | 10 (47.6) | 5 (23.8) | 2 (9.5) | 17 (81.0) | 1 (4.8) | 6 (28.6) | 3 (14.3) |
DMBA, ENNG → PM, 0.03% | 20 | 13 (65) | 16 (80) | 4 (20) | 1 (5) | 17 (85) | 3 (15) | 5 (25) | 2 (10) |
DMBA, ENNG → PM, 0.3% | 20 | 19 (95) ** | 17 (85) | 7 (35) | 1 (5) | 19 (95) | 2 (10) | 11 (55) | 8 (40) |
DMBA, ENNG → PM 1% | 21 | 19 (90.5) ** | 11(52.4) | 2 (9.5) | 2 (9.53) | 12 (57.1) | 0 (0) | 4 (19.0) | 5 (23.8) |
DMBA, ENNG → IA, 0.2% | 21 | 19 (90.5) ** | 16 (76.2) | 5 (23.8) | 4 (19.0) | 20 (95.2) | 2 (9.5) | 9 (42.9) | 9 (42.9) |
Vehicle | 5 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Vehicle → PM, 1% | 6 | 6 (100) * | 3 (50.0) | 0 (0) | 0 (0) | 3 (50.0) | 0 (0) | 0 (0) | 0 (0) |
Multiplicity (No./Rat) | |||||||||
DMBA, ENNG | 21 | - | 0.67 ± 0.80 c | 0.24 ± 0.44 | 0.14 ± 0.48 | 1.10 ± 0.64 d | 0.05 ± 0.22 | 0.33 ± 0.58 | 0.14 ± 0.36 |
DMBA, ENNG → PM, 0.03% | 20 | - | 1.25 ± 0.91 * | 0.24 ± 0.54 | 0.05 ± 0.22 | 1.55 ± 1.00 | 0.15 ± 0.37 | 0.25 ± 0.44 | 0.15 ± 0.47 |
DMBA, ENNG → PM, 0.3% | 20 | - | 1.35 ± 0.81 * | 0.35 ± 0.49 | 0.05 ± 0.22 | 1.75 ± 0.79 * | 0.10 ± 0.31 | 0.95 ± 1.19 | 0.65 ± 1.09 |
DMBA, ENNG → PM 1% | 21 | - | 0.57 ± 0.60 | 0.10 ± 0.30 | 0.14 ± 0.48 | 0.81 ± 0.81 | 0.00 ± 0.00 | 0.43 ± 1.33 | 0.33 ± 0.73 |
DMBA, ENNG → IA, 0.2% | 21 | - | 1.00 ± 0.71 | 0.24 ± 0.44 | 0.19 ± 0.40 | 1.52 ± 0.60 * | 0.10 ± 0.30 | 0.57 ± 0.75 | 0.57 ± 0.75 * |
Vehicle | 5 | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Vehicle → PM, 1% | 6 | - | 0.50 ± 0.55 | 0 | 0 | 0.50 ± 0.55 | 0 | 0 | 0 |
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Kakehashi, A.; Yoshida, M.; Tago, Y.; Ishii, N.; Okuno, T.; Gi, M.; Wanibuchi, H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins 2016, 8, 275. https://doi.org/10.3390/toxins8110275
Kakehashi A, Yoshida M, Tago Y, Ishii N, Okuno T, Gi M, Wanibuchi H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins. 2016; 8(11):275. https://doi.org/10.3390/toxins8110275
Chicago/Turabian StyleKakehashi, Anna, Midori Yoshida, Yoshiyuki Tago, Naomi Ishii, Takahiro Okuno, Min Gi, and Hideki Wanibuchi. 2016. "Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats" Toxins 8, no. 11: 275. https://doi.org/10.3390/toxins8110275
APA StyleKakehashi, A., Yoshida, M., Tago, Y., Ishii, N., Okuno, T., Gi, M., & Wanibuchi, H. (2016). Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins, 8(11), 275. https://doi.org/10.3390/toxins8110275