COMPARISON OF THE HEPATIC-EFFECTS OF NAFENOPIN AND WY-14,643 ON PEROXISOME PROLIFERATION AND CELL REPLICATION IN THE RAT AND SYRIAN-HAMSTER
COMPARISON OF THE HEPATIC-EFFECTS OF NAFENOPIN AND WY-14,643 ON PEROXISOME PROLIFERATION AND CELL REPLICATION IN THE RAT AND SYRIAN-HAMSTER
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DOI：
10.2307/3431875
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发表时间：
1993-12-01
影响因子：
10.4
通讯作者：
PRICE, RJ
中科院分区：
文献类型：
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作者：
LAKE, BG;EVANS, JG;PRICE, RJ
雄性Sprague-Dawley大鼠喂食对照饮食或含有0.05%萘芬诺平(NAF)或0.025%WY-14,643(WY)的饮食，雄性叙利亚仓鼠喂食对照饮食或含有0.25%NAF或0.025%WY的饮食，持续1、15、40和60周。 NAF 和 WY 都能使大鼠和叙利亚仓鼠的肝脏重量持续增加，并诱导过氧化物酶体脂肪酸 β-氧化。通过在第0-1周、第14-15周、第39-40周和第59-60周期间植入含有[H-3]胸苷的渗透泵来研究复制DNA合成。在给予 NAF 和 WY 1 周的大鼠中，细胞复制（通过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）增加。然而，只有 WY 在 15-60 周后细胞复制持续增加。 40周后，WY治疗的大鼠中出现了肝脏结节和肿瘤，并且60周后在所有WY治疗的大鼠和一些NAF治疗的大鼠中观察到这些病变。与大鼠相反，给予叙利亚仓鼠 NAF 和 WY 长达 60 周，对复制 DNA 合成没有明显影响，也没有观察到肝结节和肿瘤。大鼠研究表明，通过持续刺激细胞复制的一定剂量的过氧化物酶体增殖剂，可以更快地产生肝脏肿瘤，而仓鼠研究表明，过氧化物酶体增殖剂诱导的细胞复制和肝脏肿瘤形成可能存在物种差异。
Male Sprague-Dawley rats were fed control diet or diet containing 0.05% nafenopin (NAF) or 0.025% WY-14,643 (WY) and male Syrian hamsters were fed control diet or diet containing 0.25% NAF or 0.025% WY for periods of 1, 15, 40, and 60 weeks. Both NAF and WY produced a sustained increase in liver weight and induction of peroxisomal fatty acid beta-oxidation in the rat and Syrian hamster. Replicative DNA synthesis was studied by implanting osmotic pumps containing [H-3] thymidine during weeks 0-1, 14-15, 39-40, and 59-60. Cell replication, determined either as the hepatocyte labelling index or by incorporation of radioactivity into liver whole homogenate DNA, was increased in rats given NAF and WY for 1 week. However, only WY produced a sustained increased in cell replication after 15-60 weeks. After 40 weeks, liver nodules and tumors were present in WY-treated rats, and these lesions were observed in all WY-treated and some NAF-treated rats after 60 weeks. In contrast to the rat, no marked effect on replicative DNA synthesis and no liver nodules and tumors were observed in Syrian hamsters given NAF and WY for up to 60 weeks. The rat study demonstrates that liver tumors are produced more rapidly by doses of peroxisome proliferators that produce a sustained stimulation of cell replication, whereas the hamster study suggests that species differences may exist in both peroxisome proliferator-induced cell replication and liver tumor formation.