出生早期接触辛基酚对大鼠乳腺癌发病及BRCA1表达的影响

Effects of early exposure of new born rats to octylphenol on breast cancer incidence and BRCA1 expression

目的:探讨出生早期接触辛基酚(octylphenols,OP)对大鼠乳腺癌发病及乳腺癌易感基因1(breast cancer suscepti-bility gene 1,BRCA1)表达的影响。方法:雌性SD大鼠随机分为阴性对照组(Con组)、模型组(Mod组)、OP 20组、OP 40组和OP 80组。皮下注射OP 7 d后,二甲苯蒽(7,12-dimethylbenz[a]anthracene,DMBA)灌胃致癌为d 1,在d 180时处死大鼠,观察肿瘤发生情况、血雌二醇、孕酮的变化、乳腺癌组织中雌激素受体(estrogen receptor,ER)和BRCA1 mRNA及蛋白表达的改变。结果:Con组未发生肿瘤,Mod组、OP 20、OP 40和OP 80组的乳腺癌发生率分别为14/20、12/20、5/20和10/20;BRCA1表达的荧光量分别为31.54±6.15、36.27±7.57、61.69±9.96和47.38±10.45;BRCA1 mRNA表达量对数值分别为3.46±0.52、4.12±0.86、5.53±0.75和4.35±0.58,经OP处理后大鼠乳腺癌中ER表达降低。结论:OP可降低DMBA诱发乳腺癌的发生,这与上调乳腺癌中BRCA1表达、下调ER表达有关。

Objective：To investigate the effects of early exposure of new born rats to octylphenol （OP） on breast cancer incidence and breast cancer susceptibility gene 1 （BRCA1） expression. Methods：Female Sprague-Dawley rats were randomly divided into control（Con） group, model（Mod） group. OP 20, OP 40, OP 80 groups. OP was subcutaneously injected into rats from d 21 to d 27. The rats were given dimethylbenz [ a ] anthracene （DMBA） intragastrically on d 42 and were sacrificed on 180 d. The incidence of breast cancer, the changes in serum levels of estradiol and progesterone, the alteration of estrogen receptor （ER） expression and BRCA1 mRNA and protein expression in breast cancer tissues were observed. Results：No breast cancer occurred in Con group. The incidence rate of breast cancer in the Mod group, OP 20 group, OP 40 group, and OP 80 group were 70% （14/20） , 60% （12/20） , 25% （5/ 20） , and 50% （10/20） , respectively. The fluorescence intensities of BRCA1 expression were 31.54 ±6.15, 36.27 ±7.57, 61.69 ±9.96 and 47.38 ±10.45, respectively ; the logarithm value of BRCA1 mRNA expressions were 3.46 ±0. 52, 4. 12 ± 0.86, 5.53 ± 0.75, and 4.35 ±0.58, respectively. The ER expression in breast cancer tissues decreased after the rats were exposed to OP. Conclusion： OP decreased the occurrence of DMBA-induced breast cancers, which may be related with up-regulation of BRCA1 expression and downegulation of ER expression in breast cancers.