English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

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.

Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital