Prepubertal octylphenol exposure up-regulate BRCA1 expression, down-regulate ERalpha expression and reduce rat mammary tumorigenesis.
BACKGROUND
Endogenous estrogens play an important role in the development of breast cancer. Octylphenol (OP) and genistein (GEN) are estrogen-like chemicals. Prepubertal estradiol and genistein exposure can up-regulate BRCA1 mRNA in mammary gland and reduce futuer breast cancer risk. In the present study, the effects of prepubertal exposure to high-dose OP and GEN on mammary carcinogenesis and the association with the expression of BRCA1 and ERalpha were investigated.


METHODS
Prepubertal female Sprague-Dawley rats were exposed to 20, 40, 80mg/kg OP daily from postnatal day (PND) 22-28, subsequently, the rats were given a single dose of 100mg/kg 7,12-dimethylbenz [a] anthracene (DMBA) on PND42 to induce mammary tumor.


RESULTS
The incidence of DMBA-induced mammary tumors significantly decreased when rats were treated with 40mg/kg OP. BRCA1 mRNA and protein expression were found up-regulated and ERalpha expression was down-regulated in the mammary tumor when rats were exposed to 40mg/kg octylphenol.


CONCLUSIONS
Exposure 40mg/kg octylphenol can reduce later breast cancer risk in prepubertal Sprague-Dawley rats, the protective effect of OP is associated with persistent up-regulation of BRCA1 and down-regulation of ERalpha in the mammary tumor.
Peng
Jun-Hua
JH
Department of Clinical Laboratory, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, China. junhua_p@sohu.com
Zhang
Feng
F
Zhang
Hua-Xing
HX
Fan
Hong-Yan
HY
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D016588:Anticarcinogenic Agents; D019313:BRCA1 Protein; D047628:Estrogen Receptor alpha; D010636:Phenols; D012333:RNA, Messenger; C474055:octylphenol; D015127:9,10-Dimethyl-1,2-benzanthracene; D019833:Genistein