Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.
AffiliationCancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
MetadataShow full item record
AbstractThe effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.
CitationIonizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues. 1993, 14 (4):679-83 Carcinogenesis
- In vivo induction of O6-alkylguanine-DNA-alkyltransferase in response to indium-114m.
- Authors: Wilson RE, Hoyes KP, Morris ID, Sharma HL, Hendry JH, Margison GP
- Issue date: 1994 Apr
- Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent.
- Authors: Rafferty JA, Clarke AR, Sellappan D, Koref MS, Frayling IM, Margison GP
- Issue date: 1996 Feb 1
- Induction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene.
- Authors: Chinnasamy N, Rafferty JA, Margison GP, O'Connor PJ, Elder RH
- Issue date: 1997 Apr
- Tissue-specific expression and induction of human O6-alkylguanine-DNA alkyltransferase in transgenic mice.
- Authors: Rafferty JA, Fan CY, Potter PM, Watson AJ, Cawkwell L, O'Connor PJ, Margison GP
- Issue date: 1992
- Induction of rat liver O6-alkylguanine-DNA alkyltransferase following whole body X-irradiation.
- Authors: Schmerold I, Wiestler OD
- Issue date: 1986 Jan