Bischof Ina, Arnot Jon A, Jürling Heinrich, Knipschild Georg, Schlechtriem Christian, Schauerte Anna, Segner Helmut
Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany.
Centre for Fish and Wildlife Health, University of Bern, Bern, Switzerland.
Front Toxicol. 2022 Sep 23;4:1021880. doi: 10.3389/ftox.2022.1021880. eCollection 2022.
Biotransformation assays using primary hepatocytes from rainbow trout, , were validated as a reliable tool to predict bioconcentration factors (BCF) of chemicals in fish. Given the pronounced interspecies differences of chemical biotransformation, the present study aimed to compare biotransformation rate values and BCF predictions obtained with hepatocytes from the cold-water species, rainbow trout, to data obtained with hepatocytes of the warm-water species, common carp (). In a first step, we adapted the protocol for the trout hepatocyte assay, including the cryopreservation method, to carp hepatocytes. The successful adaptation serves as proof of principle that the hepatocyte biotransformation assays can be technically transferred across fish species. In a second step, we compared the intrinsic clearance rates (CL) of two model xenobiotics, benzo[a]pyrene (BaP) and methoxychlor (MXC), in trout and carp hepatocytes. The data were used to predict biotransformation rate constants (k) and BCFs, which were then compared to measured k and BCF values. The CL values of BaP and MXC did not differ significantly between trout and carp hepatocytes, but the predicted BCF values were significantly higher in trout than in carp. In contrast, the measured BCF values did not differ significantly between the two species. A possible explanation of this discrepancy is that the existing prediction models are parameterized only for trout but not for carp. Therefore, future research needs to develop species-specific extrapolation models.
使用虹鳟鱼原代肝细胞进行的生物转化试验被验证为预测鱼类中化学物质生物富集因子（BCF）的可靠工具。鉴于化学物质生物转化存在明显的种间差异，本研究旨在比较冷水物种虹鳟鱼肝细胞与温水物种鲤鱼肝细胞的生物转化速率值和BCF预测结果。第一步，我们将虹鳟鱼肝细胞试验方案，包括冷冻保存方法，应用于鲤鱼肝细胞。成功的应用证明了肝细胞生物转化试验在技术上可以跨鱼类物种转移。第二步，我们比较了两种模型外源化合物苯并[a]芘（BaP）和甲氧滴滴涕（MXC）在虹鳟鱼和鲤鱼肝细胞中的内在清除率（CL）。这些数据用于预测生物转化速率常数（k）和BCF，然后将其与实测的k和BCF值进行比较。BaP和MXC的CL值在虹鳟鱼和鲤鱼肝细胞之间没有显著差异，但预测的BCF值在虹鳟鱼中显著高于鲤鱼。相比之下，两种物种的实测BCF值没有显著差异。这种差异的一个可能解释是，现有的预测模型仅针对虹鳟鱼进行了参数化，而未针对鲤鱼。因此，未来的研究需要开发物种特异性的外推模型。
