Differential expression of O6-methylguanine-DNA methyltransferase during diethylnitrosamine-induced carcinogenesis and liver regeneration in Sprague-Dawley male rats.
Differential expression of DNA-O6MeG: protein-L-cysteine S-methyltransferase (MGMT) activity and posttranslational modification of the protein during liver regeneration and carcinogenesis were compared in Sprague-Dawley male rats after partial hepatectomy and/or single i.p injection of diethylnitrosamine (DEN, 200 mg/kg). Regenerating hepatocytes after partial hepatectomy induced MGMT transiently within 3 days; however, the induction of MGMT was persistent for 2 weeks after DEN injection, and the combined treatment of DEN and partial hepatectomy maintained the elevated MGMT level for up to 4 weeks. The increased activity was transcriptionally regulated, when analyzed by Northern blot hybridization. The major active form of MGMT protein in the partially hepatectomized or DEN-treated rats was a 26-kDa or 24-kDa species respectively, which was confirmed by Western blot analysis and gel slice assay. The biological significance of the differential induction of MGMT during partial hepatectomy or DEN-induced carcinogenesis is not obvious; however, further studies on possible posttranslational modifications of MGMT protein might shed some light on the functional aspect of MGMT induction.
Lim
I K
IK
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea. iklim@madang.ajou.ac.kr
Park
T J
TJ
Jee
J W
JW
Lee
M S
MS
Paik
W K
WK
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004052:Diethylnitrosamine; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D012333:RNA, Messenger; D004052:Diethylnitrosamine; D019853:O(6)-Methylguanine-DNA Methyltransferase