Protić-Sabljić M, Kurelec B
Mutat Res. 1983 Aug;118(3):177-89. doi: 10.1016/0165-1218(83)90141-6.
The metabolism of carcinogens in fish was examined by measuring the activation of different polycyclic aromatic hydrocarbons (PAH) by carp (Cyprinus carpio L.) liver post-mitochondrial fractions (S9) using the Salmonella typhimurium TA100 reverse mutation assay. For this study, 1 non-carcinogen, anthracene (AN), and 4 carcinogens, chrysene (CHR), benzo[a]pyrene (BaP), 3-methylcholanthrene (3MC) and 7,12-dimethylbenzanthracene (DMBA), were chosen. The bioactivating potency of the metabolic systems of carp pretreated with phenobarbital (PB), 3MC or Aroclor 1254 (ARO) were compared to uninduced carp liver. The results show that carp liver has the ability to metabolize carcinogenic PAH into mutagenic metabolites, which is enhanced when carp are pretreated with 3MC or ARO, but not with PB. A positive correlation between the induction of aryl hydrocarbon hydroxylase (AHH) activity in carp liver and the mutagenic potencies of CHR, BaP, DMBA and 3MC, has been observed. The bioactivating ability of carp liver S9 was compared with the ability of the same fractions from female Wistar rats (this study) as well as from Sprague-Dawley rats (literature data). When the mutagenic potencies of selected PAH had been normalized on the activity of BaP, the following order of mutagenic activities with S9 fractions from ARO-treated animals was obtained: (1) BaP (1) greater than DMBA (0.26) greater than 3MC (0.22) greater than CHR (0.05) greater than AN (0) for carp; (2) BaP (1) greater than 3MC (0.48) greater than CHR (0.31) greater than DMBA (0.16) greater than AN (0) for Sprague-Dawley rats; and (3) BaP (1) greater than 3MC (0.17) greater than DMBA (0.11) greater than CHR (0) = AN (0) for female Wistar rats. We conclude that carp and rats are very similar in their ability to activate carcinogenic PAH into mutagenic metabolites, which suggests that carp may be very susceptible to the carcinogenic activity of these compounds. According to our results from the mutagenicity study, as well as from the enzyme induction study, we propose the use of carp as a suitable model system for the study of chemical carcinogens.
通过使用鼠伤寒沙门氏菌TA100回复突变试验,测定鲤鱼(Cyprinus carpio L.)肝脏线粒体后组分(S9)对不同多环芳烃(PAH)的激活作用,研究了鱼类中致癌物的代谢情况。在本研究中,选择了1种非致癌物蒽(AN)和4种致癌物: Chrysene(CHR)、苯并[a]芘(BaP)、3-甲基胆蒽(3MC)和7,12-二甲基苯并蒽(DMBA)。将用苯巴比妥(PB)、3MC或多氯联苯混合物1254(ARO)预处理的鲤鱼代谢系统的生物激活能力与未诱导的鲤鱼肝脏进行比较。结果表明,鲤鱼肝脏有能力将致癌性PAH代谢为致突变代谢物,当鲤鱼用3MC或ARO预处理时,这种能力会增强,但用PB预处理则不会。已观察到鲤鱼肝脏中芳烃羟化酶(AHH)活性的诱导与CHR、BaP、DMBA和3MC的致突变能力之间呈正相关。将鲤鱼肝脏S9的生物激活能力与雌性Wistar大鼠(本研究)以及Sprague-Dawley大鼠(文献数据)相同组分的能力进行了比较。当所选PAH的致突变能力根据BaP的活性进行标准化时,对于用ARO处理的动物的S9组分,获得了以下致突变活性顺序:(1)鲤鱼:BaP(1)>DMBA(0.26)>3MC(0.22)>CHR(0.05)>AN(0);(2)Sprague-Dawley大鼠:BaP(1)>3MC(0.48)>CHR(0.31)>DMBA(0.16)>AN(0);(3)雌性Wistar大鼠:BaP(1)>3MC(0.17)>DMBA(0.11)>CHR(0)=AN(0)。我们得出结论,鲤鱼和大鼠在将致癌性PAH激活为致突变代谢物的能力方面非常相似,这表明鲤鱼可能对这些化合物的致癌活性非常敏感。根据我们在致突变性研究以及酶诱导研究中的结果,我们建议将鲤鱼用作研究化学致癌物的合适模型系统。