Potter D, Clarius T M, Wright A S, Watson W P
Shell Research Ltd., Sittingbourne Research Centre, England.
Arch Toxicol. 1994;69(1):1-7. doi: 10.1007/s002040050128.
Farm raised rainbow trout (Oncorhynchus mykiss) were exposed by various routes to benzo(a)pyrene (BP) as a representative carcinogenic polycyclic aromatic hydrocarbon (PAH). Following exposure of fish to the chemical by intraperitoneal (i.p.) injection, 32P-postlabelling studies indicated that non-feral trout were relatively resistant to the formation of BP-DNA adducts in liver. No adducts were detected in fish exposed to single doses (20 mg/kg) of BP. Multiple exposures (e.g. 2 x 25 mg/kg) were necessary in order for adducts to be detected, indicating that induction of the metabolising enzymes required for the bioactivation of BP is necessary. These studies provided reference information on DNA adducts for comparison with data from subsequent experiments at environmentally realistic low level exposures. Two types of low level aquatic exposure were carried out. The first procedure exposed fish for 30 days to a nominally constant low level (1.2 and 0.4 micrograms/l) of a homogeneous dispersion of BP in water, to simulate low level aquatic environmental exposures. Following 32P-postlabelling analysis of the liver DNA of exposed fish, BP-DNA adducts were not detected. In the second procedure, fish were exposed to a constant low level of BP (ca. 0.5 micrograms/l) for 15 days then to a pulse (60 micrograms/l) which was allowed to naturally decline (to ca. 2 micrograms/l) during a further 15 days. Following this exposure, significant levels of BP-DNA adducts were detected in livers of trout. The effect of dietary exposures was investigated by feeding trout a diet containing either 58 micrograms or 288 micrograms BP per day for 6 days, equivalent to total doses of 43 mg/kg and 216 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
养殖虹鳟鱼(Oncorhynchus mykiss)通过多种途径接触苯并(a)芘(BP),苯并(a)芘是一种具有代表性的致癌多环芳烃(PAH)。在通过腹腔注射(i.p.)将该化学物质注入鱼体后,32P后标记研究表明,非野生虹鳟鱼对肝脏中BP-DNA加合物的形成相对具有抗性。在接触单剂量(20毫克/千克)BP的鱼中未检测到加合物。为了检测到加合物,需要多次接触(例如2×25毫克/千克),这表明BP生物活化所需的代谢酶的诱导是必要的。这些研究提供了关于DNA加合物的参考信息,以便与后续在环境现实低水平暴露实验的数据进行比较。进行了两种类型的低水平水生暴露。第一种方法是将鱼暴露于名义上恒定的低水平(1.2和0.4微克/升)的BP均匀分散在水中30天,以模拟低水平水生环境暴露。对暴露鱼的肝脏DNA进行32P后标记分析后,未检测到BP-DNA加合物。在第二种方法中,鱼先暴露于恒定低水平的BP(约0.5微克/升)15天,然后暴露于一次脉冲(60微克/升),并在接下来的15天内自然下降(至约2微克/升)。经过这种暴露后,在虹鳟鱼的肝脏中检测到了显著水平 的BP-DNA加合物。通过给虹鳟鱼喂食每天含有58微克或每天288微克BP的饲料6天来研究饮食暴露的影响,这相当于总剂量为43毫克/千克和216毫克/千克。(摘要截于250字)