Induced synthesis of O6-methylguanine-DNA methyltransferase in rat hepatoma cells exposed to DNA-damaging agents.
When the rat hepatoma cell line H4IIE was treated with DNA-damaging agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ultraviolet light and gamma-rays, the O6-methylguanine-DNA methyltransferase activity increased 2 to 3 times over the level seen in non-treated cells. SDS/polyacrylamide gel electrophoresis followed by fluorography revealed that a single species of methyltransferase protein with a molecular weight of 25,500 was present in both non-treated and treated cells. Northern blot analysis using a cloned rat cDNA as a probe revealed that the enzyme activity increased because transcription of the gene was enhanced. The level of enzyme activity increased within 48 h after UV irradiation and remained at a higher level for 150 h. Following UV irradiation, the cells become more resistant than the normal cells to MNNG.
Fukuhara
M
M
Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka.
Hayakawa
H
H
Sakumi
K
K
Sekiguchi
M
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005720:Gamma Rays; D008114:Liver Neoplasms, Experimental; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008780:Methyltransferases / Q000096:biosynthesis*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014466:Ultraviolet Rays
D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase