Promotion of preneoplastic lesions and induction of CYP2B by unleaded gasoline vapor in female B6C3F1 mouse liver.
Promotion of preneoplastic lesions and induction of CYP2B by unleaded gasoline vapor in female B6C3F1 mouse liver.
复制标题
无铅汽油蒸气在雌性 B6C3F1 小鼠肝脏中促进肿瘤前病变并诱导 CYP2B。
DOI：
10.1093/carcin/14.10.2137
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发表时间：
1993
期刊：
影响因子：
4.7
通讯作者：
Goldsworthy,TL
中科院分区：
文献类型：
--
作者：
Standeven,AM;Goldsworthy,TL
一个启动-促进协议被用来测试的假设，即无铅汽油（UG）蒸汽作为一个肝肿瘤促进剂在雌性小鼠的暴露条件下，其中UG是肝癌的癌症生物测定。12日龄雌性B6 C3 F1小鼠腹腔注射N-亚硝基二乙胺（DEN，5 mg/kg），于24小时后处死。或车辆。从5-7周龄开始，小鼠通过吸入暴露于0或2039 p. p.m.的PS-6共混物UG（与癌症生物测定中使用的汽油共混物相同），6小时/天，5天/周，持续13周。肝脏中推定的癌前病变，其特征主要是H& E染色肝脏切片中的嗜碱性病灶，仅在DEN治疗的小鼠中发现。虽然在用0或2039 p. p.m. UG治疗的DEN启动小鼠中发现了相似数量的改变的肝病灶，但UG治疗显著增加了病灶的平均体积（3.2倍）和体积分数（3.6倍）。为了确定UG是否诱导CYP 2B（啮齿类动物中通常由肝肿瘤促进剂诱导的细胞色素P450亚家族），在源自上述肝脏的肝微粒体中测定了戊氧基试卤灵-O-脱烷基酶（PROD）活性。UG蒸汽使肝脏PROD活性增加了约8倍，而细胞色素P450含量仅增加了约30%。为了确定较新的UG共混物API 91-1是否具有与PS-6相似的生物学效应，用玉米油或1800 mg/kg/天PS-6或API 91-1共混物UG灌胃雌性B6 C3 F1小鼠3天。PS-6和API 91-1共混物UG相对于对照诱导了相对肝脏重量（1025%）、PROD活性（1029倍）和肝细胞标记指数（1028倍）的相似增加。这些数据表明，PS-6混合物UG蒸汽在导致肝肿瘤的暴露条件下促进肿瘤前病变并诱导雌性小鼠肝脏中的CYP 2B，并表明最近的UG混合物可能具有类似的作用。
An initiation-promotion protocol was used to test the hypothesis that unleaded gasoline (UG) vapor acts as a liver tumor promoter in female mice under exposure conditions in which UG was hepatocarcinogenic in a cancer bioassay. Twelve day old female B6C3F1 mice were injected withN-nitrosodiethylamine (DEN, 5 mg/kg, i.p.) or vehicle. Starting at 5–7 weeks of age, mice were exposed by inhalation 6 h/day, 5 days/week for 13 weeks to 0 or 2039 p.p.m. of PS-6 blend UG, the same gasoline blend used in the cancer bioassay. Putative preneoplastic lesions in liver, characterized mainly as basophilic foci in H&E-stained liver sections, were found exclusively in mice treated with DEN. While similar numbers of altered hepatic foci were found in DEN-initiated mice treated with 0 or 2039 p.p.m. UG, UG treatment significantly increased both the mean volume (3.2-fold) and the volume fraction (3.6-fold) of the foci. To determine if UG induced CYP2B, a subfamily of cytochrome P450 commonly induced by liver tumor promoters in rodents, pentoxyresorufin-O-dealkylase (PROD) activity was assayed in hepatic microsomes derived from the above livers. UG vapor increased hepatic PROD activity ∼8-fold, while increasing cytochrome P450 content only ∼30%. To ascertain if a more recent blend of UG, API 91-1, would have similar biological effects as PS-6, female B6C3F1 mice were gavaged for 3 days with corn oil or 1800 mg/kg/day PS-6 or API 91–1 blend UG. PS-6 and API 91-1 blend UG induced similar increases in relative liver weight (∼25%), PROD activity (∼9-fold) and hepatocyte labeling index (∼8-fold) relative to controls. These data demonstrate that PS-6 blend UG vapor promotes preneoplastic lesions and induces CYP2B in female mouse liver under exposure conditions in which it causes liver tumors, and suggest that a more recent blend of UG may have similar effects.