Murata Y, Denda A, Obara T, Yokose Y, Konishi Y
Department of Oncological Pathology, Nara Medical College, Japan.
Exp Pathol. 1987;32(1):41-53. doi: 10.1016/s0232-1513(87)80026-9.
The utility of gamma-glutamyltranspeptidase (gamma-GTP) as an enzyme marker during pancreatic acinar cell carcinogenesis in rats was assessed by measuring its enzyme-histochemical performance in pancreatic acinar cell lesions induced by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) and/or azaserine in partially-pancreatectomized Fischer 344 and Wistar rats. Rats were given a single intravenous injection of 4-HAQO (10 or 7 mg/kg body weight) 3 days after partial pancreatectomy followed by intraperitoneal injections of azaserine (30 mg/kg) once a week for 10 weeks, or the same treatment without azaserine. The animals were sacrificed at 3, 6, 10, 12 and 18 months. 4-HAQO predominantly induced basophilic foci in Fischer rats, while in Wistar rats acidophilic foci and acidophilic hyperplastic nodules were predominant. A preferential enhancement of the induction of acidophilic foci and hyperplastic nodules was exhibited in Fischer rats following co-administration with azaserine. Normal acinar cells were positive for gamma-GTP. 90 to 100% of basophilic foci were either negative or slightly positive for gamma-GTP, whilst 68 to 98% of acidophilic foci were positive. The gamma-GTP activities of acidophilic hyperplastic nodules were more variable between nodules than within nodules, and either co-administration of azaserine or extension of experimental duration time appeared to increase the gamma-GTP positive nodules. Between the gamma-GTP positive and decreased nodules, no histological but some morphometrical differences were observed. As far as the nodules induced by 4-HAQO in Fischer rats were concerned, all of the gamma-GTP decreased nodules had thin fibrous capsules and exhibited ultrastructurally more atypia than the positive ones. Present study thus revealed that gamma-GTP is neither a useful nor invariable enzyme marker during pancreatic acinar cell carcinogenesis in rats.
通过测量γ-谷氨酰转肽酶（γ-GTP）在部分胰腺切除的Fischer 344和Wistar大鼠中由4-羟基氨基喹啉1-氧化物（4-HAQO）和/或重氮丝氨酸诱导的胰腺腺泡细胞病变中的酶组织化学表现，评估其作为大鼠胰腺腺泡细胞癌变过程中酶标志物的效用。部分胰腺切除3天后，给大鼠单次静脉注射4-HAQO（10或7 mg/kg体重），随后每周腹腔注射一次重氮丝氨酸（30 mg/kg），持续10周，或进行相同处理但不注射重氮丝氨酸。在3、6、10、12和18个月时处死动物。4-HAQO在Fischer大鼠中主要诱导嗜碱性病灶，而在Wistar大鼠中嗜酸性病灶和嗜酸性增生性结节占主导。在Fischer大鼠中，与重氮丝氨酸联合给药后，嗜酸性病灶和增生性结节的诱导有优先增强。正常腺泡细胞γ-GTP呈阳性。90%至100%的嗜碱性病灶γ-GTP呈阴性或弱阳性，而68%至98%的嗜酸性病灶呈阳性。嗜酸性增生性结节的γ-GTP活性在结节之间比在结节内变化更大，重氮丝氨酸联合给药或延长实验持续时间似乎会增加γ-GTP阳性结节。在γ-GTP阳性和降低的结节之间，未观察到组织学差异，但观察到一些形态计量学差异。就Fischer大鼠中由4-HAQO诱导的结节而言，所有γ-GTP降低的结节都有薄的纤维包膜，并且在超微结构上比阳性结节表现出更多的异型性。因此，本研究表明，γ-GTP在大鼠胰腺腺泡细胞癌变过程中既不是有用的也不是恒定的酶标志物。
