Moser G J, Wolf D C, Sar M, Gaido K W, Janszen D, Goldsworthy T L
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA.
Toxicol Sci. 1998 Jan;41(1):77-87. doi: 10.1006/toxs.1997.2366.
Chronic exposure to methyl tertiary butyl ether (MTBE) altered the rodent tumor incidence of endocrine-sensitive tissues and decreased the incidence of estrogen-dependent uterine cystic hyperplasia in mice. To test the hypothesis that changes in the incidence of tumors in female B6C3F1 mice after MTBE exposure are secondary to endocrine alterations, we exposed female mice to the carcinogenic dose of MTBE vapor (8000 ppm) for 3 or 21 days or 4 or 8 months under conditions similar to a previous 2-year bioassay. MTBE exposure significantly decreased body weight gain and ovary and pituitary weight at 4 and 8 months and uterine weight at all time points. After 8 months of exposure, MTBE significantly increased the length of the estrous cycle by increasing the mean number of days in both the estrus and the nonestrus stages. Histological evaluation of H&E-stained tissues showed a decrease in the number of uterine glands after subchronic MTBE exposure. DNA synthesis, as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU), was decreased in uterine glandular and luminal epithelial cells after MTBE exposure for 3 or 21 days or 4 or 8 months. MTBE exposure decreased the number of epithelial layers in the cervix and vagina at all time points. DNA synthesis was decreased in cervical and vaginal epithelium after 21 days of MTBE. Decreased zona reticularis of adrenal glands was found after 4 and 8 months of MTBE exposure without changes in BrdU incorporation. MTBE did not competitively bind to estrogen receptor. MTBE exposure did not alter serum estrogen levels or alter the location or intensity of estrogen receptor immunoreactivity in the uterus, cervix, and vagina. These data indicate that while MTBE exposure causes multiple endocrine-related tissue and cellular responses, these effects are not mediated through the estrogen receptor.
长期接触甲基叔丁基醚（MTBE）会改变啮齿动物内分泌敏感组织的肿瘤发生率，并降低小鼠雌激素依赖性子宫囊性增生的发生率。为了验证MTBE暴露后雌性B6C3F1小鼠肿瘤发生率的变化继发于内分泌改变这一假说，我们在与之前一项2年生物测定相似的条件下，将雌性小鼠暴露于致癌剂量的MTBE蒸气（8000 ppm）中3天或21天，或4个月或8个月。MTBE暴露在4个月和8个月时显著降低体重增加、卵巢和垂体重量，在所有时间点均降低子宫重量。暴露8个月后，MTBE通过增加发情期和非发情期的平均天数显著延长发情周期长度。对苏木精-伊红（H&E）染色组织的组织学评估显示，亚慢性MTBE暴露后子宫腺数量减少。通过5-溴-2'-脱氧尿苷（BrdU）掺入法测定，MTBE暴露3天或21天、4个月或8个月后，子宫腺上皮细胞和腔上皮细胞中的DNA合成减少。MTBE暴露在所有时间点均减少宫颈和阴道的上皮层数。MTBE暴露21天后，宫颈和阴道上皮中的DNA合成减少。MTBE暴露4个月和8个月后发现肾上腺网状带减少，而BrdU掺入无变化。MTBE不与雌激素受体竞争性结合。MTBE暴露未改变血清雌激素水平，也未改变子宫、宫颈和阴道中雌激素受体免疫反应性的位置或强度。这些数据表明，虽然MTBE暴露会引起多种与内分泌相关的组织和细胞反应，但这些效应并非通过雌激素受体介导。
