Skip Navigation


ToxSci Advance Access originally published online on November 4, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
76/2/291    most recent
kfg253v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Randi, A. S.
Right arrow Articles by Kleiman de Pisarev, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Randi, A. S.
Right arrow Articles by Kleiman de Pisarev, D. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 76, 291-298 (2003)
Copyright © 2003 by the Society of Toxicology

CARCINOGENICITY

Hexachlorobenzene-Induced Early Changes in Ornithine Decarboxylase and Protein Tyrosine Kinase Activities, Polyamines and c-Myc, c-Fos and c-Jun Proto-Oncogenes in Rat Liver

Andrea S. Randi*, Susana Hernández*,{dagger}, Laura Alvarez*, Marcela Sánchez*,{ddagger}, Marta Schwarcz{dagger},{ddagger} and Diana L. Kleiman de Pisarev*,1

* Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, (CP 1121), Buenos Aires, Argentina; {dagger} Facultad de Medicina, Universidad Abierta Interamericana, (CP 1147), Buenos Aires, Argentina; and {ddagger} Ciclo Básico Común, Universidad de Buenos Aires, (CP 1053), Buenos Aires, Argentina

Hexachlorobenzene (HCB) is a lipophilic chemical compound that is widely distributed in the environment. HCB is known to cause liver tumors in experimental animals. In the present study the in vivo effect of HCB treatment on ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) activities, free polyamine content, and c-Myc, c-Fos, and c-Jun protein levels in rat liver were investigated. HCB (1000 mg/kg body weight) increased hepatic immunodetectable c-Myc, c-Fos, and c-Jun levels after 6 h, and ODC activity and spermine and putrescine content after 18 and 24 h, while maximum stimulation of PTK activity occurred at 12 h. PTK and ODC activities varied in a dose-dependent manner. The time-course of c-Myc, c-Fos, and c-Jun protein levels was different for each proto-oncogene. They were all elevated at the second day of treatment, while only c-Fos and c-Jun remained elevated after 10 days of HCB exposure. These data jointly suggest that the increase in ODC activity may be the consequence of proto-oncogene induction. The alterations in PTK activity suggest that the growth factor signal transduction pathway may be involved in the regulation of the proto-oncogene levels or/and ODC activity. The decrease in PTK activity after the first day, even in the presence of {alpha}-D-Difluoromethylornithine (DFMO), an inhibitor of ODC activity, suggests that it is not regulated by polyamines. These results may be relevant to the early molecular events involved in HCB tumor promoter activity in rat liver.

Key Words: hexachlorobenzene; rat liver; ODC activity; PTK activity; polyamine content; proto-oncogene levels.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.