H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats

Shahin, M., Moore, M. R., Worrall, S., Smith, B. L., Seawright, A. A. and Prakash, A. S. (1998) H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats. Biochemical And Biophysical Research Communications, 250 2: 491-497. doi:10.1006/bbrc.1998.9341


Author Shahin, M.
Moore, M. R.
Worrall, S.
Smith, B. L.
Seawright, A. A.
Prakash, A. S.
Title H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats
Journal name Biochemical And Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 1998
Sub-type Article (original research)
DOI 10.1006/bbrc.1998.9341
Volume 250
Issue 2
Start page 491
End page 497
Total pages 7
Language eng
Abstract 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 (iv) tail vein or by intragastric (ig) route, A third group was given a weekly dose of 6 mg of APT for 3 weeks by the ig route corresponding to acute dosing. Both chronic iv and ig dosed animals showed ischemic tubular necrosis in the kidney but only iv dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed ig 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 ig rats or the tumor-bearing iv rats. However, the mammary glands of a fourth group of rats, which received APT by iv 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. (C) 1998 Academic Press.
Keyword Biochemistry & Molecular Biology
Biophysics
Ptaquiloside
Bracken Fern
H-ras
P53
Dna Adduct
Tnf Alpha
Adenocarcinoma
Oncogenes
Mutations
Bracken
Carcinomas
Tumors
Cancer
Gene
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Mon, 13 Aug 2007, 10:42:27 EST