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

Pub. Date : 2017

PMID : 28785378






6 Functional Relationships(s)
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1 Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital. Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus
2 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). Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus
3 Hepatocellular carcinomas (HCCs) were found in PB-treated Ogg1-/- mice, while Ogg1+/+ animals developed only hepatocellular adenomas (HCAs) at the same rate. Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus
4 This was coordinated with PB-induced significant elevation of 8-OHdG formation in DNA and cell proliferation in adjacent liver of Ogg1-/- mice. Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus
5 Treatment of Ogg1-/- mice with PB resulted in significant elevation of cell proliferation in the liver. Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus
6 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. Phenobarbital 8-oxoguanine DNA-glycosylase 1 Mus musculus