Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital
Joint Authors
Ishii, Naomi
Okuno, Takahiro
Fujioka, Masaki
Fukushima, Shoji
Wei, Min
Kakehashi, Anna
Wanibuchi, Hideki
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-07-13
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
The carcinogenic potential of phenobarbital (PB) was assessed in a mouse line carrying a mutant Mmh allele of the Mmh/Ogg1 gene encoding the enzyme oxoguanine DNA glycosylase (Ogg1) responsible for the repair of 8-hydroxy-2′-deoxyguanosine (8-OHdG).
Mmh homozygous mutant (Ogg1−/−) and wild-type (Ogg1+/+) male and female, 10-week-old, mice were treated with 500 ppm PB in diet for 78 weeks.
Hepatocellular carcinomas (HCCs) were found in PB-treated Ogg1−/− mice, while Ogg1+/+ animals developed only hepatocellular adenomas (HCAs) at the same rate.
This was coordinated with PB-induced significant elevation of 8-OHdG formation in DNA and cell proliferation in adjacent liver of Ogg1−/− mice.
Proteome analysis predicted activation of transcriptional factor Nrf2 in the livers and HCAs of PB-administered Ogg1+/+ mice; however, its activation was insufficient or absent in the livers and HCCs of Ogg1−/− mice, respectively.
Significant elevation of phase I and II metabolizing enzymes was demonstrated in both Ogg1−/− and Ogg1+/+ animals.
Treatment of Ogg1−/− mice with PB resulted in significant elevation of cell proliferation in the liver.
These results indicate that PB induced progression from HCA to HCC in Ogg1−/− mice, due to persistent accumulation of DNA oxidative base modifications and suppression of Nrf2-mediated oxidative stress response, resulting in significant elevation of cell proliferation.
American Psychological Association (APA)
Kakehashi, Anna& Ishii, Naomi& Okuno, Takahiro& Fujioka, Masaki& Wei, Min& Fukushima, Shoji…[et al.]. 2017. Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1196221
Modern Language Association (MLA)
Kakehashi, Anna…[et al.]. Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-16.
https://search.emarefa.net/detail/BIM-1196221
American Medical Association (AMA)
Kakehashi, Anna& Ishii, Naomi& Okuno, Takahiro& Fujioka, Masaki& Wei, Min& Fukushima, Shoji…[et al.]. Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1196221
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1196221