Genetic toxicity assessment using liver cell models: past,present, and future

ABSTRACT

Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.     

Changes in iodine status among US adults, 2001–2012

Urinary iodine concentrations (UICs) in the US have been reported to be stable since 1988–1994, although those in selected subgroups remained low. We aimed to investigate iodine status among adults (≥20 years) by two different criteria of assessing iodine deficiency in population. Utilizing National Health and Nutrition Examination Surveys 2001–2012, we conducted linear logistic regressions adjusting for covariates. The prevalence of <50?μg/L UIC was higher in women than in men; increased from 11.6% (2001–2004) to 13.2% (2009–2012) at the national level and in young adults, non-Hispanic blacks (NHBs) and non-users of iodine-containing supplements (all, p?<0.05); the adjusted odds ratios (95%CI) in young adults (1.54 [1.11–2.15], p =?0.0007) and NHBs (1.70 [1.15–2.52], p =?0.0078). Median UICs confirm women and NHBs being in borderline iodine status. Recognizing the critical consequence of iodine deficiency particularly in women and NHBs, regular monitoring of iodine status is important for public health in the US.