Adenosine Kinase Deficiency Increases Susceptibility to a Carcinogen.

Background: Adenosine kinase (ADK) is a key regulator of hepatic metabolism. Its deficiency in the liver causes hepatic steatosis and methylation defects. In this study, we investigated whether reduced ADK expression affects the susceptibility of the liver to a carcinogen. Methods: We investigated ADK expression in samples from 11 liver cancer patients. We used transgenic Adk-tg mice with reduced hepatic ADK to study their susceptibility to a carcinogen. We exposed 45 Adk-tg and 21 wild-type (WT) mice to the carcinogen diethylnitrosamine (DEN) and the tumor promoter phenobarbital (PB) and examined the survival and body weight. Results: Seven of 11 patients with liver cancer had reduced ADK expression. A Kaplan-Meier survival curve showed a significantly increased mortality rate of DEN/PB-exposed Adk-tg mice compared with WT mice. Conclusions: Reduced hepatic ADK increases the susceptibility to the acute toxic effects of a carcinogen. Low hepatic ADK might be a risk factor and biomarker for cancer development.