Price R J, Evans J G, Lake B G
BIBRA Toxicology International, Carshalton, Surrey, UK.
Food Chem Toxicol. 1992 Nov;30(11):937-44. doi: 10.1016/0278-6915(92)90178-n.
Male Sprague-Dawley rats were fed control or 0.1% nafenopin diet and male Syrian hamsters were fed control or 0.25% nafenopin diet for periods of 7 and 54 days. Nafenopin treatment produced a sustained increase in liver weight and induction of hepatic peroxisomal and microsomal fatty acid-oxidizing enzyme activities, with a greater effect being observed in the rat. Replicative DNA synthesis was studied by implanting osmotic pumps containing [3H]thymidine during study days 0-7 and 47-54. Cell replication, determined either as the hepatocyte labelling index or by incorporation of radioactivity into liver whole homogenate DNA, was increased in rats given nafenopin for 7 and 54 days. In contrast to the rat, no significant effect on replicative DNA synthesis was observed in the Syrian hamster. These results provide further evidence for species differences in hepatic peroxisome proliferation, with the Syrian hamster being less responsive than the rat. Furthermore, while peroxisome proliferators produce hyperplasia in rat and mouse liver, these data suggest that they may not have any marked effect on hepatic replicative DNA synthesis in the Syrian hamster.
将雄性斯普拉格-道利大鼠分别喂以对照饮食或含0.1%萘芬诺平的饮食，将雄性叙利亚仓鼠分别喂以对照饮食或含0.25%萘芬诺平的饮食，持续7天和54天。萘芬诺平处理使肝脏重量持续增加，并诱导肝脏过氧化物酶体和微粒体脂肪酸氧化酶活性升高，在大鼠中观察到的效应更大。在研究的第0 - 7天和第47 - 54天，通过植入含有[3H]胸腺嘧啶核苷的渗透泵来研究复制性DNA合成。以肝细胞标记指数或通过将放射性掺入肝脏全匀浆DNA来确定的细胞复制，在给予萘芬诺平7天和54天的大鼠中增加。与大鼠相反，在叙利亚仓鼠中未观察到对复制性DNA合成有显著影响。这些结果为肝脏过氧化物酶体增殖的种属差异提供了进一步的证据，叙利亚仓鼠的反应性低于大鼠。此外，虽然过氧化物酶体增殖剂在大鼠和小鼠肝脏中产生增生，但这些数据表明它们可能对叙利亚仓鼠的肝脏复制性DNA合成没有任何显著影响。
