Lack of effects of postnatal exposure to a mixture of aryl hydrocarbon-receptor agonists on the development of methylnitrosourea-induced mammary tumors in Sprague-Dawley rats
Lack of effects of postnatal exposure to a mixture of aryl hydrocarbon-receptor agonists on the development of methylnitrosourea-induced mammary tumors in Sprague-Dawley rats
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DOI：
10.1080/15287390490483818
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发表时间：
2004-09-24
影响因子：
2.6
通讯作者：
Tsang, BK
中科院分区：
文献类型：
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作者：
Desaulniers, D;Leingartner, K;Tsang, BK
有人担心，生命早期接触有机氯，包括芳烃受体 (AhR) 激动剂，可能会导致长期影响并增加患乳腺癌的风险。我们的目的是测试出生后接触 2,3,7,8-四氯二苯并二恶英 (TCDD) 类化学物质的混合物是否会调节甲基亚硝基脲 (MNU) 诱发的乳腺肿瘤的发展。雌性在 1、5、10、15 和 20 天时灌胃含有 3 种非邻位多氯联苯 (PCB)、6 种多氯二苯并二恶英 (PCDDS) 和 7 种多氯二苯并呋喃 (PCDF) 的混合物。这些剂量相当于人类婴儿在出生后 24 天内通过母乳摄入量的 0、1、10、100 或 1000 倍。 1000x 处理的大鼠亚组和对照组在 21 天龄时被处死，以评估乳腺发育、细胞死亡和增殖。在预先暴露于混合物（MNU-0、MNU-1、MNU-10、MNU-100、MNU-1000）的 MNU（50 日龄时腹腔注射 30 mg/kg 体重）诱导的大鼠中评估乳腺肿瘤的发展。当乳腺肿瘤直径达到1cm时或当大鼠年龄大于或等于32周时处死大鼠。对所有可触及和显微镜下病变（n = 1563）的乳腺整体进行了组织学分类和分组为良性、导管内增殖或恶性的分析。对青春期开始年龄（阴道开口）和动情周期没有明显影响。尽管在 1000 倍治疗的 21 日龄大鼠中，增殖细胞核抗原 (PCNA) 阳性乳腺细胞显着减少，但对乳腺形态和肿瘤发展没有长期剂量反应影响。总之，出生后接触 AhR 激动剂混合物对 MNU 引发的乳腺肿瘤的发展没有显着影响。
There are concerns that early life exposure to organochlorines, including aryl hydrocarbon receptor (AhR) agonists, may lead to long-term effects and increase the risk of developing breast cancer. Our objective was to test if postnatal exposure to a mixture of 2,3, 7,8-tetrachlorodibenzodioxin (TCDD)-like chemicals would modulate the development of methylnitrosourea (MNU)-induced mammary tumors. Females received by gavage a mixture containing 3 non-ortho-polychlorinated biphenyls (PCBs), 6 polychlorinated dibenzodioxins (PCDDS), and 7 polychlorinated dibenzofurans (PCDFs), at 1, 5, 10, 15, and 20 d of age. The doses were equivalent to 0, 1, 10, 100, or 1000 times the amount ingested through breast milk by a human infant during its first 24 d of life. Subgroups of 1000x treated rats and controls were sacrificed at 21 d of age for assessment of mammary-gland development, cell death, and proliferation. Mammary-tumor development was assessed in MNU (30 mg/kg body weight ip at 50 days of age)-induced rats pre-exposed to the mixture (MNU-0, MNU-1, MNU-10, MNU-100, MNU-1000). Rats were sacrificed when their mammary tumors reached 1 cm in diameter, or when the rats reached greater than or equal to32 wk of age. Mammary-gland whole mounts were analyzed with all palpable and microscopic lesions (n=1563) histologically classified and grouped as benign, intraductal proliferations, or malignant. There were no marked effects on age at onset of puberty (vaginal opening) and estrous cyclicity. Despite a significant decrease in proliferating cell nuclear antigen (PCNA)-positive mammary cells in 1000x treated 21-d-old rats, there were no long-term dose-response effects on mammary-gland morphology and tumor development. In conclusion, postnatal exposure to the mixture of AhR agonists had no significant effects on the development of MNU-initiated mammary tumors.