Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice.

2.50
Hdl Handle:
http://hdl.handle.net/10146/55493
Title:
Lack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice.
Authors:
Puatanachokchai, Rawiwan; Kakuni, Masakazu; Wanibuchi, Hideki; Kinoshita, Anna; Kang, Jin Seok; Salim, Elsayed I.; Morimura, Keiichirou; Tamano, Seiko; Merlino, Glenn T.; Fukushima, Shoji
Abstract:
Phenobarbital (PB), a rodent non-genotoxic carcinogen, showed hormesis, biphasic effects on rat liver carcinogenesis. To test the hypothesis that the hormesis earlier observed for PB induced hepatocarcinogenesis might also exist in the TGF-alpha transgenic mice model, one which is highly susceptible to carcinogenesis, the carcinogenic or promotion effects of a wide range of phenobarbital (PB) concentrations were investigated. Two weeks after a single i.p. dose of 5 mg /kg bw of diethylnitrosamine (DEN) to 15 day old mice, animals were treated with diet containing PB at doses of 0, 2, 15 or 500 ppm. The incidence and multiplicity of tumors, including hepatocellular adenomas and carcinomas, were significantly increased by the high dose of PB, but no significant difference among the groups receiving 2 and 15 ppm for liver tumors when compared to DEN alone group. The proliferating cell nuclear antigen indices for liver tumors and surrounding hepatocytes in high dose PB treated mice were significantly increased, but no change was noted at the lower doses. The total cytochrome P450 content in the liver was also elevated by 500 ppm of PB, while hepatic 8-OHdG levels demonstrated no significant change. In conclusion, PB at high dose enhances DEN-induced hepatocarcinogenesis in TGF-alpha transgenic mice, but low doses lack any significant effects. One possible mechanism of phenobarbital carcinogenicity might be influenced by cytochrome P450 system exhibiting a strong promoting activity for liver of mice.
Citation:
Asian Pac. J. Cancer Prev. 2006, 7 (2):274-278
Journal:
Asian Pacific Journal of Cancer Prevention : APJCP
Issue Date:
16-Mar-2009
URI:
http://hdl.handle.net/10146/55493
PubMed ID:
16839222
Additional Links:
http://www.apocp.org/journal_of_cancer_prevention_volume_7.php
Type:
Article
Language:
en
Description:
KEYWORDS-CLASSIFICATION: administration & dosage;Animals;Anticonvulsants;Carcinogenicity Tests;Carcinogens;chemically induced;Diethylnitrosamine;Dose-Response Relationship,Drug;genetics;Japan;Liver Neoplasms;mechanisms of carcinogenesis;metabolism;Mice;Mice,Transgenic;pathology;Phenobarbital;Research;toxicity;Transforming Growth Factor alpha;
ISSN:
1513-7368
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorPuatanachokchai, Rawiwan-
dc.contributor.authorKakuni, Masakazu-
dc.contributor.authorWanibuchi, Hideki-
dc.contributor.authorKinoshita, Anna-
dc.contributor.authorKang, Jin Seok-
dc.contributor.authorSalim, Elsayed I.-
dc.contributor.authorMorimura, Keiichirou-
dc.contributor.authorTamano, Seiko-
dc.contributor.authorMerlino, Glenn T.-
dc.contributor.authorFukushima, Shoji-
dc.date.accessioned2009-03-16T08:51:17Z-
dc.date.available2009-03-16T08:51:17Z-
dc.date.issued2009-03-16T08:51:17Z-
dc.identifier.citationAsian Pac. J. Cancer Prev. 2006, 7 (2):274-278en
dc.identifier.issn1513-7368-
dc.identifier.pmid16839222-
dc.identifier.urihttp://hdl.handle.net/10146/55493-
dc.descriptionKEYWORDS-CLASSIFICATION: administration & dosage;Animals;Anticonvulsants;Carcinogenicity Tests;Carcinogens;chemically induced;Diethylnitrosamine;Dose-Response Relationship,Drug;genetics;Japan;Liver Neoplasms;mechanisms of carcinogenesis;metabolism;Mice;Mice,Transgenic;pathology;Phenobarbital;Research;toxicity;Transforming Growth Factor alpha;en
dc.description.abstractPhenobarbital (PB), a rodent non-genotoxic carcinogen, showed hormesis, biphasic effects on rat liver carcinogenesis. To test the hypothesis that the hormesis earlier observed for PB induced hepatocarcinogenesis might also exist in the TGF-alpha transgenic mice model, one which is highly susceptible to carcinogenesis, the carcinogenic or promotion effects of a wide range of phenobarbital (PB) concentrations were investigated. Two weeks after a single i.p. dose of 5 mg /kg bw of diethylnitrosamine (DEN) to 15 day old mice, animals were treated with diet containing PB at doses of 0, 2, 15 or 500 ppm. The incidence and multiplicity of tumors, including hepatocellular adenomas and carcinomas, were significantly increased by the high dose of PB, but no significant difference among the groups receiving 2 and 15 ppm for liver tumors when compared to DEN alone group. The proliferating cell nuclear antigen indices for liver tumors and surrounding hepatocytes in high dose PB treated mice were significantly increased, but no change was noted at the lower doses. The total cytochrome P450 content in the liver was also elevated by 500 ppm of PB, while hepatic 8-OHdG levels demonstrated no significant change. In conclusion, PB at high dose enhances DEN-induced hepatocarcinogenesis in TGF-alpha transgenic mice, but low doses lack any significant effects. One possible mechanism of phenobarbital carcinogenicity might be influenced by cytochrome P450 system exhibiting a strong promoting activity for liver of mice.en
dc.language.isoenen
dc.relation.urlhttp://www.apocp.org/journal_of_cancer_prevention_volume_7.phpen
dc.subjectCancer risk assessmenten
dc.subjecthepatocarcinogenesisen
dc.subjectphenobarbitalen
dc.subjectTGFαen
dc.subjecttransgenic mouse modelen
dc.subject.meshAnimals-
dc.subject.meshAnticonvulsants-
dc.subject.meshCarcinogenicity Tests-
dc.subject.meshCarcinogens-
dc.subject.meshDiethylnitrosamine-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMice-
dc.subject.meshMice, Transgenic-
dc.subject.meshPhenobarbital-
dc.subject.meshTransforming Growth Factor alpha-
dc.titleLack of promoting effects of phenobarbital at low dose on diethylnitrosamine-induced hepatocarcinogenesis in TGF-alpha transgenic mice.en
dc.typeArticleen
dc.identifier.journalAsian Pacific Journal of Cancer Prevention : APJCPen
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