Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

2.50
Hdl Handle:
http://hdl.handle.net/10541/100201
Title:
Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.
Authors:
Wilson, Rosemary E; Hoey, Brigid M; Margison, Geoffrey P
Abstract:
The 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.
Affiliation:
Cancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues. 1993, 14 (4):679-83 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Apr-1993
URI:
http://hdl.handle.net/10541/100201
DOI:
10.1093/carcin/14.4.679
PubMed ID:
8472332
Type:
Article
Language:
en
ISSN:
0143-3334
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWilson, Rosemary Een
dc.contributor.authorHoey, Brigid Men
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-06-03T11:57:16Z-
dc.date.available2010-06-03T11:57:16Z-
dc.date.issued1993-04-
dc.identifier.citationIonizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues. 1993, 14 (4):679-83 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid8472332-
dc.identifier.doi10.1093/carcin/14.4.679-
dc.identifier.urihttp://hdl.handle.net/10541/100201-
dc.description.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.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBrain-
dc.subject.meshEnzyme Induction-
dc.subject.meshKidney-
dc.subject.meshLiver-
dc.subject.meshLung-
dc.subject.meshMale-
dc.subject.meshMethyltransferases-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Inbred DBA-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRNA, Messenger-
dc.subject.meshRadiation Dosage-
dc.subject.meshSpleen-
dc.subject.meshTime Factors-
dc.subject.meshWhole-Body Irradiation-
dc.titleIonizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalCarcinogenesisen

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