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Formation of Glycidyl Methacrylate-DNA Adducts in vivo

Biomedical and Environmental Sciences 1999年第2期12卷 95-102页

作者： FANG FU-DE LEI HAI-XIN ZUO JIN TAN MING-JIA AND XU JIAN-NING (Institute of Basic Medical Sciences, Chinese Academy of Medical Scicnces,Beijing 100005, China Instituse of Occupational Medicine, Chinese Academy of Preverntive Medicine, Beijing 100050, China) 中国医学科学院基础医学所北京 100005 中国预防医学科学院职业病医学所北京 100050 中国医学科学院基础医学所北京中国预防医学科学院职业病医学所北京

In in vivo test, rats were orally administrated with glycidyl methacrylate (GMA) at respective doses of 250 mg/kg, 125 mg/kg and 62. 5 mg/kg, 31. 25 mg/kg and solvent as control for 14 days. DNA adducts produced in the liver, kidney, blood and testis were analyzed by RP-HPLC and nuclease P1 mediated 32 P-postlabelling method. Results showed that several potential GMA-DNA adducts were formed in various organs (4 adducts in blood, 3 adducts in liver and kidney, 1 adduct in testis). A linear dose-response relationship was observed within certain dose levels. The relative adduct labeling values failed to further increase any more when the concentration went up to 125 mg/kg. The order of adduct level with GMA was kidney, liver, blood and testis. The GMA adduct N3methacrylate-2-hydroxypropyl-dCMP was found in kidney, liver and blood. These results indicated that GMA could react with negatively charged centers on DNA and form GMA-DNA adducts. If carcinogerrinduced DNA damage exceeds the ability of repair systems, gene mutation is ***, study on molecular mechanism of gene mutation induced by DNA adducts is not only an important part of chemical-carcinogenesis, but also provides information on critical biomarkers for monitoring human exposure to genetic toxins.

关键词： Animals Carcinogens DNA Adducts DNA Damage DNA Repair Dose-Response Relationship Drug epoxy compounds Male Methacrylates Mutagenesis Phosphorus Radioisotopes Rats Rats Wistar Research Support Non-U.S. Gov't

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