Characterization of O6-methylguanine-DNA methyltransferase in transgenic mice introduced with the E. coli ada gene.

Abstract

The characteristics of O6-methylguanine-DNA methyltransferase (O6-MTase) produced in transgenic mice, in which the introduced E. coli ada gene was expressed under the control of the metallothionein promoter, were investigated. Liver extracts from transgenic homozygotes showed approximately 3 times the control activity, a marked increase of up to about 8 times the non-transgenic control levels being observed 10 h after zinc treatment. Examination of the substrate specificity of the enzyme revealed that the activity in the transgenic mice is due to the introduced foreign gene. The enzyme possessed methylphosphotriester-DNA methyltransferase as well as O6-MTase, characteristic of the E. coli Ada protein. Comparison of differences in biological response between transgenic and non-transgenic mice after treatment with the alkylating carcinogen methylnitrosourea (MNU) at various doses revealed transgenic mice to be more capable of repairing O6-MTase activity, only showing signs of exhaustion at very high levels of exposure. In non-transgenic mice, on the other hand, the basal level of O6-MTase was low, and the activity was hardly detectable when the animals were treated with MNU.

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@article{Nakatsuru1991CharacterizationOO, title={Characterization of O6-methylguanine-DNA methyltransferase in transgenic mice introduced with the E. coli ada gene.}, author={Yoko Nakatsuru and Susumu Matsukuma and Masayuki Sekiguchi and Takashi Ishikawa}, journal={Mutation research}, year={1991}, volume={254 3}, pages={225-30} }