关键词: DNA损伤, 彗星试验, 多器官, 遗传毒性

Abstract: OBJECTIVE: Comet assays were conducted on Sprague Dawley rats treated with four chemicals with different mechanisms of action:p-chloroaniline,sodium chloride,acetaminophen and gentamicin. METHODS: Rats were orally exposed to p-chloroaniline[37.5,75 and 150 mg/(kg·d)],sodium chloride[500,1 000 and 2 000 mg/(kg·d)],acetaminophen[20,100 and 500 mg/(kg·d)],vehicle controls,and intramuscular-injected gentamicin[20,40,and 80 mg/(kg·d)] for three consecutive days (0,24 and 45 h),as well as orally treated with the positive control (EMS,200 mg/kg) for 24 and 45 h. Liver,stomach,and kidney were sampled approximately 3 h after the last dosing. After preparation of single cell suspensions,slides were prepared for lysis,unwinding,electrophoresis,neutralization,and DNA staining for comet visualization and image analysis. Histopathological examination of liver and kidney was respectively conducted for the two target-organ toxicity chemicals (acetaminophen and gentamicin). RESULTS: Among the four chemicals,p-chloroanilin produced positive results in liver,stomach,and kidney,while sodium chloride,acetaminophen,and gentamicin were all negative in liver,stomach,and kidney. Inflammation,degeneration,or necrosis of liver was noted in all the acetaminophen dosing groups. CONCLUSION: Collectively,known genotoxic compounds and non-genotoxic compounds with and without target-organ toxicity were used to verify the sensitivity and specificity of the multi-organ comet assay,which is expected to provide technical reference for the popularization of alkaline comet assay in vivo in the field of genotoxicity evaluation for new drugs.

Key words: DNA damage, comet assay, multi-organs, genotoxicity