Differential responses on energy metabolic pathway reprogramming between genotoxic and non-genotoxic hepatocarcinogens in rat liver cells.

Differential responses on energy metabolic pathway reprogramming between genotoxic and non-genotoxic hepatocarcinogens in rat liver cells. J Toxicol Pathol. 2019 Oct;32(4):261-274 Authors: Ito Y, Nakajima K, Masubuchi Y, Kikuchi S, Saito F, Akahori Y, Jin M, Yoshida T, Shibutani M Abstract To clarify difference in the responses on the reprogramming of metabolism toward carcinogenesis between genotoxic and non-genotoxic hepatocarcinogens in the liver, rats were repeatedly administered genotoxic hepatocarcinogens (N-nitrosodiethylamine, aflatoxin B1, N-nitrosopyrrolidine, or carbadox) or non-genotoxic hepatocarcinogens (carbon tetrachloride, thioacetamide, or methapyrilene hydrochloride) for 28, 84, or 90 days. Non-genotoxic hepatocarcinogens revealed transcript expression changes suggestive of suppressed mitochondrial oxidative phosphorylation (OXPHOS) after 28 days and increased glutathione S-transferase placental form-positive (GST-P+) foci downregulating adenosine triphosphate (ATP) synthase subunit beta, mitochondrial precursor (ATPB), compared with genotoxic hepatocarcinogens after 84 or 90 days, suggesting that non-genotoxic hepatocarcinogens are prone to suppress OXPHOS from the early stage of treatment, which is in contrast to genotoxic hepatocarcinogens. Both genotoxic and non-genotoxic hepatocarcinogens upregulated glycolytic enzyme genes and increased cellular membrane solute carrier family 2, facilitated glucose transporte...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research