Kostka G, Kopeć-Szlezak J, Palut D
Zakład Toksykologii Srodowiskowej, Państwowy Zakład Higieny, Warszawa.
Rocz Panstw Zakl Hig. 1996;47(1):87-94.
The aim of present studies was to describe the effect of two organochlorine pesticides: nuarimol and DDT on the changes in rat liver, proposed in the literature to be useful endpoints in screening of non-genotoxic hepatocarcinogens and/or liver tumor promoters. The effects on the following endpoints: mitogenesis (DNA synthesis and mitotic activity), hepatomegaly as well as histological changes in rat liver have been investigated. Male Wistar rats received nuarimol or DDT in one, five and fourteen daily oral administration of the doses of 125 and 12 mg/kg b.w. day-1 respectively. In the case of both pesticides the effects observed consisted of hepatomegaly and hepatocyte proliferation (DNA synthesis and mitotic activity), although our studies indicated several distinct differences in the hepatic response between nuarimol, on the one hand and DDT on the other. The differences were reflected in the character and the basal rate of hepatocyte proliferation. Nuarimol elicited rapid but transient wave of hepatocyte proliferation during the first day of exposure. As opposite to nuarimol, DDT induced sustained hepatocyte proliferation during experimental period (14 days). Moreover, DDT induced evident focal necrosis and abnormal mitoses whereas nuarimol caused only slight vacuolated cytoplasm. Thus it can be concluded that nuarimol induced in rat liver direct mitogenic effect. On the other hand, DDT which is well known hepatocarcinogen, was found to produce mitogenic effect appearing to be related to regenerative response, since histological signs of necrosis were apparent.
氟节胺和滴滴涕对大鼠肝脏变化的影响,文献中提出这些变化是筛选非遗传毒性肝癌致癌物和/或肝脏肿瘤促进剂的有用终点。研究了对以下终点的影响:有丝分裂(DNA合成和有丝分裂活性)、肝肿大以及大鼠肝脏的组织学变化。雄性Wistar大鼠分别以125和12 mg/kg体重·天-1的剂量每日口服一次、五次和十四次给予氟节胺或滴滴涕。对于这两种农药,观察到的影响包括肝肿大和肝细胞增殖(DNA合成和有丝分裂活性),尽管我们的研究表明氟节胺和滴滴涕在肝脏反应方面存在几个明显差异。这些差异反映在肝细胞增殖的特征和基础速率上。氟节胺在暴露的第一天引起快速但短暂的肝细胞增殖浪潮。与氟节胺相反,滴滴涕在实验期间(14天)诱导持续的肝细胞增殖。此外,滴滴涕诱导明显的局灶性坏死和异常有丝分裂,而氟节胺仅导致轻微的细胞质空泡化。因此可以得出结论,氟节胺在大鼠肝脏中诱导直接的有丝分裂作用。另一方面,众所周知的肝癌致癌物滴滴涕被发现产生的有丝分裂作用似乎与再生反应有关,因为坏死的组织学迹象很明显。