利用转基因动物对金属硫蛋白抗化学致癌的机理探讨

Metallothionein (MT) is believed to be a cytoprotective protein, but its primary function has not been identified. It is interesting to understand the roles of MT in physiological and pathogenic processes in order to treat the disease related to MT distinctions and potential therapeutic usage of MT. We had preciously fund that MT has a preventive function on skin carcinogenesis induced by polycyclic aromatic hydrocarbon (PAH). The purpose of this project is to study the protective mechanisms by using MT gene knocked out mice. We have found several MT new functions. (1) The MT can be induced by PAH. The wild-type mice MT content in liver of the wild-type mice was significantly induced one fold vs. control liver after 24 h with PAHs treatment. This is the first time of report that MT can be induced by PAH by our knowledge. (2) MT showed protective functions against PAH-induced genetic damages measured as micronuclei formation, chromosome aberration, H-ras mutation, Indicated that MT plays a role in the initiation stage of carcinogenesis. (3) PAH also acted as a blood toxicant. The mice erythrocyte decreased after PAH administration in MT (-/-) mice. (4) MT (-/-) mice are extremely susceptible to the two-stage carcinogenesis caused by DMBA/TPA. The anti-tumor related inflammative function of MT has been suggested. (5) MT played a role in prevention against PAH-induced immunotoxicity. As the immune function is important in cancer, the function of MT in immune regulation should be studied futhure. Taking together, MT provided a multiple functions to prevent chemical carcinogenesis including genetic/immune/inflammation pathways.

阐明金属硫蛋白抗化学致癌的分子机制，保护DNA和抗突变能力为目标，观察MT影响多环芳﨑NA加合物的形成和抗癌基因等致突变的能力，确定MT的作用。.