McGuinness E E, Morgan R G, Wormsley K G
Dept of Therapeutics, Ninewells Hospital, University of Dundee, Scotland.
Gut. 1987;28 Suppl(Suppl):207-12. doi: 10.1136/gut.28.suppl.207.
We have previously shown that rats fed raw soya flour (RSF) for more than four months develop hyperplastic foci of pancreatic acinar cells, which undergo malignant change if feeding RSF is continued throughout the life of the animals. The tendency to undergo malignant change is augmented by the additional use of a genotoxic carcinogen such as azaserine. The present study has sought to examine the reversibility of the focal neoplastic change in the pancreas. Rats fed RSF for 24 weeks and then given a diet not containing soya flour (NSC) had a normal pancreas when killed after 60 weeks of study. When RSF was fed for only 36 weeks, however, some of the rats developed pancreatic cancer even though the diet had been switched to NSC. Similarly, while azaserine in the dose used in the present study does not produce pancreatic cancer in our strain of Wistar rats, coincident administration of RSF for 12 weeks (but not for six weeks) resulted in progression to pancreatic adenoma. Although change from RSF to NSC after 30 weeks resulted in rapid reduction in pancreatic weight and content of RNA, neoplastic foci persisted and became frankly malignant. We conclude that phenotypic reversion to normal of the RSF diet- and azaserine-treated rat pancreas is only possible if RSF alone is fed continuously for not more than about 24 weeks or six weeks if the rats have been exposed to a pancreatic initiating carcinogen.
我们之前已经表明,用生大豆粉(RSF)喂养大鼠超过四个月会导致胰腺腺泡细胞出现增生性病灶,如果在动物的整个生命过程中持续喂食RSF,这些病灶会发生恶性变化。额外使用基因毒性致癌物如偶氮丝氨酸会增强发生恶性变化的倾向。本研究旨在检验胰腺局灶性肿瘤变化的可逆性。用RSF喂养24周,然后给予不含大豆粉的饮食(NSC)的大鼠,在研究60周后处死时胰腺正常。然而,当仅用RSF喂养36周时,尽管饮食已改为NSC,但一些大鼠仍患上了胰腺癌。同样,虽然本研究中所用剂量的偶氮丝氨酸在我们的Wistar大鼠品系中不会引发胰腺癌,但同时给予RSF 12周(而非6周)会导致进展为胰腺腺瘤。尽管在30周后从RSF改为NSC会导致胰腺重量和RNA含量迅速降低,但肿瘤病灶持续存在并明显恶变。我们得出结论,只有在单独连续喂食RSF不超过约24周,或者如果大鼠已接触胰腺启动致癌物,则不超过6周的情况下,RSF饮食和偶氮丝氨酸处理的大鼠胰腺才有可能表型恢复正常。