[Diethylstilbestrol intervention in carcinogenesis of breast cancer in wistar rats].
OBJECTIVE
As a synthesized estrogenic drug, diethylstilbestrol (DES) is generally used to cure diseases like climacteric period syndrome and osteoporosis due to estrogen insufficient, but its effect on mammary gland epithelial cells is still unclear. This study was to observe the effect of DES on dimethylbenzanthracene (DMBA)-induced carcinogenesis of breast cancer in Wistar rats.


METHODS
A total of 90 Wistar rats were equally divided into control, DES(1), DMBA, DES(1) plus DMBA, DES(2) plus DMBA, and DES(3) plus DMBA groups. The rats were perfused with DMBA at a dose of 100 mg/kg on Days 1 and 30, and DES at a dose of 0.1 mg x kg(-1) x d(-1) (DES(1)), 0.2 mg x kg(-1) x d(-1) (DES(2)), or 0.4 mg x kg(-1) x d(-1) (DES(3)), respectively. All rats were killed after 44 weeks. The morphology of the breast tissue was observed; silver-binding nucleolar organizer regions (AgNOR) were counted; proliferating cell nuclear antigen (PCNA) staining intensity index (SII), the protein expression of Bcl-2, and C-erbB-2 were detected by SP immunohistochemistry.


RESULTS
Among 15 rats with breast cancer carcinogenesis, 2 came from DES(1) plus DMBA group and 13 from DMBA group. AgNOR count, and the levels of PCNA SII, Bcl-2, and C-erbB-2 were higher in DES(1) group than in control group; AgNOR count, and the levels of PCNA SII, Bcl-2, and C-erbB-2 were significantly lower in DES(2) plus DMBA group than in DES(3) plus DMBA group and DES(1) plus DMBA group (P < 0.05), but there was no significant difference between DES(3) plus DMBA group and DES(1) plus DMBA group (P > 0.05).


CONCLUSIONS
Low dose of DES can cause hyperplasia of the mammary gland in Wistar rats but not lead to carcinogenesis. During the DMBA-induced carcinogenesis of breast cancer in Wistar rats, low dose of DES can promote the hyperplasia and carcinogenesis of the mammary gland, medium dose of DES can inhibit the proliferation of mammary epithelial cells, but the effect may weaken while increasing the dose of DES.
Chen
Hu
H
Department of General Surgery, The First Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050013, P. R. China.
Geng
Cui-Zhi
CZ
Kuang
Gang
G
Wang
Gui-Lan
GL
Fan
Zhong-Lin
ZL
Wu
Xiang-De
XD
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D015127:9,10-Dimethyl-1,2-benzanthracene; D034961:Antigens, Nuclear; D002273:Carcinogens; D004054:Diethylstilbestrol; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; C051963:nucleolar organizer region associated proteins