The Effect Of Reproduction In Carcinogenesis Of DMBA Induced Breast Cancer In Female SD Rat

Objective: With the development of society and economy, more and more women postpone the age of the reproduction, the age of being mother is becoming older and older. Meanwhile, the incidence of breast cancer rises quickly. Breast cancer is considered as outcome of many etiology factors effect, it is well known that reproduction is one of the risk factors. Many epidemiology researches have certified that nulliparous women are at increased risk of breast cancer compared with parous women.We study the effect of reproduction and the age of reproduction to epithelial cells of mammary gland induced by DMBA in SD rat, which can help us clear the effect of occurrence and development of breast cancer, to renew the idea of prevention and cure of breast cancer, and direct clinical work to breast cancer.Methods:1.80 healthy female virgin SD rats of 8 weeks,40 healthy female virgin SD rats of 36 weeks and 10 healthy male SD rats of 12 weeks. Each category was radomedly divided into 2 groups: control group ( non DMBA) and experimental group (DMBA):①20 female virgin SD rats of 8 weeks (control group of early reproduction) ;②20 female virgin SD rats of 8 weeks (experimental group of early reproduction);③20 female virgin SD rats of 36 weeks (control group of late reproduction);④20 female virgin SD rats of 36 weeks (experimental group of late reproduction);⑤20 female virgin SD rats of 8 weeks (control group of nulliparity) ;⑥20 female virgin SD rats of 8 weeks (experimental group of nulliparity)2.40 female virgin SD rats of 8 weeks and 40 female virgin SD rats of 36 weeks are mated with male SD rats.When female virgin SD rats breeded, 20 female virgin SD rats of 8 weeks and 20 female virgin SD rats of 36 weeks are feeded with 10mg/100g DMBA twice, as well as another 20 female virgin SD rats of 8 weeks.3.All female rats were killed after 24 weeks. The morphological change was observed in macroscopic observation. Breast tissue get from rats were imbedded with paraffin then stained with H-E Silver-binding nucleoar organizer regions (AgNOR) were counted and the expressions of C-erbB-2,PCNA,Ki-67and MCM2 were detected by S-P method.4.The data was organized and processed with SPSS13.0 statistical software.Results:1.Incidence:There have 32 rats with breast cancer in 55 survival rats, 19 in experimental group of nulliparity (DMBA), 3 in experimental group of early reproduction (DMBA), 10 in experimental group of late reproduction (DMBA), 0 in all control groups. It shows statistical difference between group of nulliparity (DMBA) and group of early reproduction (DMBA),group of nulliparity (DMBA) and group of late reproduction (DMBA),group of early reproduction (DMBA) and group of late reproduction (DMBA). (p=9.59×10-7,p=0.014,p=0.015)2.Latency: group of nulliparity (DMBA)(10.25±0.83)weeks; group of early reproduction (DMBA)(17.25±3.20)weeks; group of late reproduction (DMBA)(14.50±0.96)weeks. It shows statistical difference between group of nulliparity (DMBA) and group of early reproduction (DMBA),group of nulliparity (DMBA) and group of late reproduction (DMBA),group of early reproduction (DMBA) and group of late reproduction (DMBA). (p=0.001,p=1.90×10-6,p=0.014) 3. Diameter of tumor: group of nulliparity (DMBA()2.86±0.54)cm; group of early reproduction (DMBA)(2.65±1.67)cm; group of late reproduction (DMBA)(2.41±0.50)cm.It shows no statistical difference in three groups.(p=1.00,p=0.54,p=0.81)4.The AgNOR in rat breast epithelioglandular: The AgNOR in rat breast epithelioglandular of group of nulliparity (DMBA)(7.52±1.24)higher than that of group of early reproduction (DMBA)(3.52±3.00)and group of late reproduction (DMBA)(4.76±1.20).(P=0.009,P=0.008)It shows no statistical difference between group of early reproduction (DMBA) and group of late reproduction.(p=0.287)5.The positive expression of C-erbB-2 in rat breast epithelioglandular: The positive expression of C-erbB-2 in rat breast epithelioglandular of group of nulliparity (DMBA) (16/20) higher than that of group of early reproduction (DMBA()3/18)and group of late reproduction (DMBA()5/17) (p=0.00023,p=0.003). It shows no statistical difference between group of early reproduction (DMBA) and group of late reproduction.(p=0.443)6.The positive expression of PCNA in rat breast epithelioglandular: The positive expression of PCNA in rat breast epithelioglandular of group of nulliparity (DMBA) (14/20) higher than that of group of early reproduction (DMBA)(3/18)and group of late reproduction (DMBA)(4/17)(p=0.001,p=0.008 ) . It shows no statistical difference between group of early reproduction (DMBA) and group of late reproduction.(p=0.691)7.The positive expression of Ki-67 in rat breast epithelioglandular: The positive expression of Ki-67 in rat breast epithelioglandular of group of nulliparity (DMBA) (17/20) higher than that of group of early reproduction (DMBA)(3/18)and group of late reproduction (6/17)(DMBA)(p=5.1×10-5,p=0.003). It shows no statistical difference between group of early reproduction (DMBA) and group of late reproduction.(p=0.264)8.The positive expression of MCM2 in rat breast epithelioglandular: The positive expression of MCM2 in rat breast epithelioglandular of group of nulliparity (DMBA) (16/20) higher than that of group of early reproduction (DMBA()3/18)and group of late reproduction (DMBA()6/17)(.p=0.00023,p=0.008 ) It shows no statistical difference between group of early reproduction (DMBA) and group of late reproduction.(p=0.264)Conclusion:1.The animal model of breast cancer in rat can be made by given twice DMBA intragastric administration, to simulate the incidence and development of human breast tumor, and used to study the mechanism in breast carcinogenesis and do many intervention studies.2.Reproduction can decline the incidence of breast cancer which induced by DMBA. It can put off the reproductive experimental group onset time.3.The sensitivity to DMBA in group of nulliparity (DMBA) is greater than group of reproduction, the incidence of breast cancer in group of nulliparity (DMBA) is higher than group of reproduction (DMBA).4.The sensitivity to DMBA in group of late reproduction (DMBA) is greater than group of early reproduction (DMBA), the incidence of breast cancer in group of late reproduction (DMBA) is higher than group of early reproduction (DMBA).5.AgNOR,C-erbB-2,PCNA,Ki-67,MCM2 show that reproduction gives SD rats better prognosis.