Fischer G, Altmannsberger M, Schauer A, Katz N
J Cancer Res Clin Oncol. 1983;106(1):53-7. doi: 10.1007/BF00399897.
The antihistaminic drug methapyrilene hydrochloride, which induces liver tumors in rats, was administrated orally to female Wistar rats. The animals were killed after 21, 38, 77, 119, 181, and 196 days. The activities of adenosine-5-triphosphatase (ATPase) and gamma-glutamyltranspeptidase (gamma-GT) in the liver were investigated histochemically. At 21 days, a homogeneous decrease of ATPase activity as well as a slight increase of gamma-GT activity was found in the periportal zone. Additionally, after 38 days hepatocellular foci with reappearance of gamma-GT occurred mainly in the periportal zone. After 119 days, foci with increased gamma-GT activity as well as a significant reduction of ATPase activity could be observed predominantly in the periportal region. The size and number of these putative preneoplastic foci were increased according to the time of administration of methapyrilene hydrochloride. After 181 days of methapyrilene hydrochloride treatment three of five animals developed hyperplastic nodules with corresponding alterations of enzyme activities. Methapyrilene hydrochloride-a carcinogen with an unknown mechanism of reaction-produces preneoplastic changes that are analogous to the well known preneoplastic lesions in the liver observed after administration of other carcinogenic agents.
将诱导大鼠肝脏肿瘤的抗组胺药盐酸美吡拉敏经口给予雌性Wistar大鼠。在21、38、77、119、181和196天后处死动物。采用组织化学方法研究肝脏中腺苷-5-三磷酸酶（ATP酶）和γ-谷氨酰转肽酶（γ-GT）的活性。在21天时，门周区发现ATP酶活性均匀降低以及γ-GT活性略有增加。此外，38天后，γ-GT重新出现的肝细胞灶主要出现在门周区。119天后，主要在门周区域可观察到γ-GT活性增加的灶以及ATP酶活性的显著降低。这些假定的癌前灶的大小和数量随着盐酸美吡拉敏给药时间的延长而增加。在盐酸美吡拉敏治疗181天后，五只动物中有三只出现了增生性结节，并伴有相应的酶活性改变。盐酸美吡拉敏——一种反应机制不明的致癌物——产生的癌前变化类似于给予其他致癌剂后在肝脏中观察到的众所周知的癌前病变。
