Formation of glycidyl methacrylate-DNA adducts in vivo.
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 32P-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 N3-methacrylate-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 carcinogen induced 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.
Fang
F D
FD
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Lei
H X
HX
Zuo
J
J
Tan
M J
MJ
Xu
J N
JN
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D018736:DNA Adducts / Q000187:drug effects*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology / Q000633:toxicity*; D016296:Mutagenesis / Q000235:genetics; D010761:Phosphorus Radioisotopes; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D018736:DNA Adducts; D004852:Epoxy Compounds; D008689:Methacrylates; D010761:Phosphorus Radioisotopes; C007870:glycidyl methacrylate