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[In vivo micronuclei and gene mutation induced by DEN in the lacZ transgenic mouse]
Li Zhan1, Li-Shi Zhang, Li Wang
1National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To assess mutagenicity of N-nitrosodiethylamine (DEN) in vivo using the lacZ transgenic mouse (Muta Mouse).
Methods:
LacZ gene was recovered through in vitro packing. Mutant frequencies (MFs) in the lacZ gene of liver, lung and bladder were examined after intraperitoneal treatment with DEN (25mg/kg per week x 4). Simultaneously, the clastogenicity of DEN was evaluated by the peripheral blood micronucleus assay.
Results:
The mean frequency of micronucleated reticulocytes (MNRETs) did not increase by the treatment with DEN. The MFs increase above spontaneous levels were apparent in liver and lung, with respectively 6.13 - and 3.66 fold increase. The MF of lacZ of bladder was of the background level.
Conclusion:
Liver and lung are target organ of genotoxicity in vivo induced by DEN with different sensitivity.
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