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 t...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 induced.Therefore, 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.展开更多
文摘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 induced.Therefore, 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.
