In the assessment of genotoxicity of environmental chemicals, a battery approach has been recommended. The testing battery in general includes bacterial and rodent mammalian cells as target organisms. Data generated from our comparative evaluation of these approaches indicated that when comparison of the same or two different well-defined end points, but involving different metabolic activation systems, was made, qualitative difference in response was observed. To enable one to rationally and critically evaluate the risk of environmental chemicals to humans and to perform the evaluation in an expeditious as well as economical manner, we propose to establish permanent human liver cell lines with the eventual aim of providing a battery of human liver cell lines for risk assessment. Specifically, we propose in Phase I of this project to establish several normal continuously replicating human liver cell lines from human primary hepatocyte cultures. Phase II of this project will be the full characterization and validation of these established human liver cell lines as components of a testing battery for risk assessment.This work is primarily relevant to the programs sponsored by NCI, Cancer Treatment Program, Toxicology_development of human somatic cell mutagenesis system; and by NIEHS.National Institute of Environmental Health Sciences (NIEHS)
