Enhancement of 06-Methylguanine-DNA-Methyltransferase Activity Induced by Various Treatments in Mammalian Cells1
نویسنده
چکیده
The 06-methylguanine-DNA-methyltransferase (methyltransferase) activity was determined in a rat hepatoma cell line after treatment with ultraviolet or 7-irradiation, heat treatment, or incubation with c/'.vdiamminedichloroplatinum(ll), 2-methyI-9-hydroxyeIIipticinium, or bleomycin. The assay measured the removal of 0*-methylguanine from 'IIalkylated DNA by cellular extracts. The results show that 48 h after the various treatments, the methyltransferase activity is increased by 2to 5-fold. This increase is due to de novo specific protein synthesis. It is not related to a modification of the cell cycle parameters, as a similar enhancement is observed in plateau-phase cells treated with ionizing radiations or m-dichlorodiammineplatinum(II). The increase of the methyltransferase activity measured using an alkylated substrate represents an actual increase of the active molecules in the cells, as the mutation frequency is much lower in cells treated with A'-methyl-/V'-nitro-/V-nitrosoguanidine 48 h after an irradiation (3 Gy) than in nonirradiated cells. This induction of the methyltransferase was not observed in Chinese hamster ovary cells after 7-irradiation, and therefore it does not seem to occur in cells which have a low constitutive level of O'-methylguanine
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