Abstract: Objective To investigate the effects of different dosage lead exposure on DNA damage, the expression of growth arrest and DNA damage inducible gene 153(GADD 153) in primarily cultured rath ippocam palneurons.Methods Wistar rat hippocampal neurons were primarily cultured for 7 days.Neurons in lead acetate groups were exposed to 0.2, 1.0, and 10 mol/L lead acetate.Subsequently, hippocampal neurons in each group were cultured for 24 hours.The effects of lead on DNA damage was measured with cometassay, and GADD 153 expression was measured using we stern blot analysis.Results Olive tail moment in all lead treated groups and the percentage of DNA in the tail in 1.0 μmol/L and 10 mol/L lead acetate groups were significantly increased compared with those of the control group(P<0.05).In addition, the percentage of tailDNA was higher in the 0.2 μmol/L lead acetate group compared with that of the control group (P>0.05).After incubation with 0.2, 1.0, and 10 μmol/L lead acetate for 24 hours, GADD 153 expression gradually decreased with the increase of lead acetate concentration (1.0-10 μmol/L).Conclusion Lead exposure to primarily cultured rat hippocampal neurons results in dose-dependent disturbed cellular homeostasis, including DNA damage and reduced GADD 153 expression.