Li M H, Hansen L G
Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign 61801, USA.
Fundam Appl Toxicol. 1996 Oct;33(2):282-93. doi: 10.1006/faat.1996.0166.
An extract of landfill soil containing high levels of polychlorinated biphenyls (PCBs) was refined by alumina-charcoal column chromatography to remove coplanar PCBs and high relative levels of PCDFs. Both extracts were administered ip in corn oil to immature female rats on Days 21 and 22 of age. Rats were terminated on Day 23 and organ weights, enzyme activities, and serum thyroxine (T4) were measured. The change in characteristics caused by charcoal-stripping was confirmed by comparing hepatic microsomal 7-ethoxyresorufin O-deethylase (EROD), 7-pentoxyresorufin O-depentylase (PROD), 7-benzyloxyresorufin O-dearylase (BROD), and UDP glucuronyl transferase (UDPGT) activities. EROD and 4-nitrophenol (4-NP) UDPGT activities, estimates of aryl hydrocarbon (Ah) receptor agonists present, peaked at 140 mg/kg soil extract, declining at 210 mg/kg; these activities in rats treated with the charcoal-refined soil extract were not induced at low doses, but increased linearly from 70 to 210 mg/kg. Conversely, PROD and BROD activities were modestly induced at 7 to 70 mg/kg of either soil extract; however, at higher doses induction was threefold higher in rats receiving the charcoal-filtered extract. Liver weights increased in a pattern similar to EROD induction. At all doses, the weak uterotropic response was greater in rats receiving the charcoal-filtered extract, probably due to removal of antiestrogenic Ah receptor agonists by the charcoal. Serum total T4 declined similarly in rats receiving either extract to about 40% of control values at the highest doses. Short-term integrated bioassays such as this are useful in detecting multiple complex interactions and can be used to define the net effects of mixtures with changing compositions for improved risk assessment.
通过氧化铝 - 活性炭柱色谱法对含有高浓度多氯联苯(PCBs)的垃圾填埋场土壤提取物进行提纯,以去除共平面多氯联苯和高相对含量的多氯二苯并呋喃(PCDFs)。在幼龄雌性大鼠21日龄和22日龄时,将两种提取物都溶解于玉米油中经腹腔注射给药。在23日龄时处死大鼠,并测量器官重量、酶活性和血清甲状腺素(T4)。通过比较肝微粒体7 - 乙氧基异吩恶唑酮 - O - 脱乙基酶(EROD)、7 - 戊氧基异吩恶唑酮 - O - 脱戊基酶(PROD)、7 - 苄氧基异吩恶唑酮 - O - 脱苄基酶(BROD)和UDP - 葡糖醛酸基转移酶(UDPGT)的活性,证实了活性炭去除处理所引起的特性变化。EROD和4 -硝基苯酚(4 - NP)UDPGT活性(作为存在的芳烃(Ah)受体激动剂的指标)在土壤提取物剂量为140 mg/kg时达到峰值,在210 mg/kg时下降;用活性炭提纯后的土壤提取物处理的大鼠中,这些活性在低剂量时未被诱导,但在70至210 mg/kg范围内呈线性增加。相反,PROD和BROD活性在两种土壤提取物剂量为7至70 mg/kg时均有适度诱导;然而,在较高剂量时,接受活性炭过滤提取物的大鼠中的诱导程度高出三倍。肝脏重量的增加模式与EROD诱导相似。在所有剂量下,接受活性炭过滤提取物的大鼠中较弱的子宫促生长反应更大,这可能是由于活性炭去除了抗雌激素的Ah受体激动剂。接受任何一种提取物的大鼠血清总T4在最高剂量时均同样下降至对照值的约40%。这样的短期综合生物测定对于检测多种复杂相互作用很有用,并且可用于确定成分不断变化的混合物的净效应,以改进风险评估。