Human bioassays to assess environmental genotoxicity: development of a DNA repair assay in HepG2 cells.
A direct assessment of the effects of environmental chemicals on human health has been hampered by the lack of suitable experimental systems. We have recently employed a human liver cell line (HepG2) to assess the biological effects of pollutants at both cellular and DNA levels. A Neutral Red dye uptake assay was used to assess potential cytotoxic effects of xenobiotics. DNA damage was quantified using an unscheduled DNA synthesis assay that measures repair that is induced following exposure to genotoxic compounds. HepG2 cells responded to the known mutagens, 4-nitroquinoline N-oxide and methylmethane sulfonate, both in the Neutral Red assay for cytotoxicity and two DNA repair assays for genotoxicity (monitored autoradiographically or by liquid scintillation counting). The HepG2 DNA repair and cytotoxicity assays also responded to an extract (containing polycyclic aromatic hydrocarbons) of sediment obtained from a polluted site in the Great Lakes. Results indicate that this system can be deployed further to assess potential cyto- and genotoxicity of pollutants. The development of human cell culture assays is a critical step towards a full assessment of the risk that such pollutants pose to human health.
Naji-Ali
F
F
Department of Chemistry and Biochemistry, University of Windsor, Ontario, Canada.
Hasspieler
B M
BM
Haffner
D
D
Adeli
K
K
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D001345:Autoradiography; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D006114:Great Lakes Region; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009499:Neutral Red / Q000378:metabolism; D011083:Polycyclic Compounds; D018675:Toxicity Tests / Q000379:methods*
D004785:Environmental Pollutants; D011083:Polycyclic Compounds; D009499:Neutral Red; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate