Shahin M, Moore M R, Worrall S, Smith B L, Seawright A A, Prakash A S
National Research Centre for Environmental Toxicology (NRCET), University of Queensland, Australia.
Biochem Biophys Res Commun. 1998 Sep 18;250(2):491-7. doi: 10.1006/bbrc.1998.9341.
Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen. The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (i.v.) tail vein or by intragastric (i.g.) route. A third group was given a weekly dose of 6 mg of APT for 3 weeks by the i.g. route corresponding to acute dosing. Both chronic i.v. and i.g. dosed animals showed ischemic tubular necrosis in the kidney but only i.v. dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed i.g. animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors. No mutations were found in the H-ras and p53 genes in the mammary glands of either the i.g. rats or the tumor-bearing i.v. rats. However, the mammary glands of a fourth group of rats, which received APT by i.v. and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model.
蕨菜（蕨属植物）会导致放牧动物患膀胱癌和食道癌，是一种疑似人类致癌物。致癌成分ptaquiloside（PT）在被激活为二烯酮（APT）时会形成DNA加合物，最终导致肿瘤。两组雌性斯普拉格-道利大鼠分别通过静脉（i.v.）尾静脉或胃内（i.g.）途径，每周给予3毫克APT的慢性剂量，持续10周。第三组通过胃内途径每周给予6毫克APT的剂量，持续3周，相当于急性给药。慢性静脉注射和胃内给药的动物肾脏均出现缺血性肾小管坏死，但只有静脉注射给药的动物发生了乳腺癌。急性胃内给药的动物肝脏产生凋亡小体，骨髓中血细胞前体坏死，肾脏出现缺血性肾小管坏死，但未发生肿瘤。在胃内给药大鼠或患癌静脉注射大鼠的乳腺中，未发现H-ras和p53基因的突变。然而，第四组通过静脉注射接受APT并在肿瘤发生前处死的大鼠，其乳腺中H-ras的第58和59密码子存在Pu到Pu和Pu到Py的双突变。这项研究表明，给药途径在ptaquiloside暴露导致的疾病表现性质中起作用。除了证实APT在PT诱导的致癌作用中的作用外，我们的发现还表明H-ras的激活是PT致癌模型中的早期事件。
