Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay.

2.50
Hdl Handle:
http://hdl.handle.net/10541/88617
Title:
Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay.
Authors:
Jackson, Peta E; Cooper, Donald P; Meyer, T A; Wood, M; Povey, Andrew C; Margison, Geoffrey P
Abstract:
Female SWR mice were treated with 1,2-dimethylhydrazine (DMH: 6.8 mg/kg i.p. injection) once weekly for up to 10 weeks, a dosing regime that produced tumours principally within the distal colon (Jackson et al., 1999. Carcinogenesis 20, 509-513). O(6)-Methylguanine (O(6)-MeG) levels, measured using a simple [3H]-based O(6)-alkylguanine-DNA alkyltransferase (ATase) inactivation assay, ranged from 0.6 to 16.7 fmol/microg DNA with: (i) highest levels in the distal colon; and (ii) higher levels after 68 mg/kg total DMH than 6.8 mg/kg DMH. Basal ATase activity varied between 0.97 and 1.22 fmol/microg DNA within the colon but was not associated with adduct levels or tumour induction. After 6.8 mg/kg DMH, the half life of O(6)-MeG in colonic tissue was 36-42 h whereas after 68 mg/kg DMH, t1/2 was approximately 25, 57 and 96 h in the proximal, mid and distal colon, respectively. Tumour induction was thus associated with the levels and persistence of O(6)-MeG in the distal colon.
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay. 2000, 115 (3):205-12 Toxicol. Lett.
Journal:
Toxicology Letters
Issue Date:
5-Jun-2000
URI:
http://hdl.handle.net/10541/88617
DOI:
10.1016/S0378-4274(00)00193-4
PubMed ID:
10814890
Type:
Article
Language:
en
ISSN:
0378-4274
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJackson, Peta Een
dc.contributor.authorCooper, Donald Pen
dc.contributor.authorMeyer, T Aen
dc.contributor.authorWood, Men
dc.contributor.authorPovey, Andrew Cen
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2009-12-29T10:40:25Z-
dc.date.available2009-12-29T10:40:25Z-
dc.date.issued2000-06-05-
dc.identifier.citationFormation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay. 2000, 115 (3):205-12 Toxicol. Lett.en
dc.identifier.issn0378-4274-
dc.identifier.pmid10814890-
dc.identifier.doi10.1016/S0378-4274(00)00193-4-
dc.identifier.urihttp://hdl.handle.net/10541/88617-
dc.description.abstractFemale SWR mice were treated with 1,2-dimethylhydrazine (DMH: 6.8 mg/kg i.p. injection) once weekly for up to 10 weeks, a dosing regime that produced tumours principally within the distal colon (Jackson et al., 1999. Carcinogenesis 20, 509-513). O(6)-Methylguanine (O(6)-MeG) levels, measured using a simple [3H]-based O(6)-alkylguanine-DNA alkyltransferase (ATase) inactivation assay, ranged from 0.6 to 16.7 fmol/microg DNA with: (i) highest levels in the distal colon; and (ii) higher levels after 68 mg/kg total DMH than 6.8 mg/kg DMH. Basal ATase activity varied between 0.97 and 1.22 fmol/microg DNA within the colon but was not associated with adduct levels or tumour induction. After 6.8 mg/kg DMH, the half life of O(6)-MeG in colonic tissue was 36-42 h whereas after 68 mg/kg DMH, t1/2 was approximately 25, 57 and 96 h in the proximal, mid and distal colon, respectively. Tumour induction was thus associated with the levels and persistence of O(6)-MeG in the distal colon.en
dc.language.isoenen
dc.subjectColonic Canceren
dc.subject.mesh1,2-Dimethylhydrazine-
dc.subject.meshAnimals-
dc.subject.meshCarcinogens-
dc.subject.meshColon-
dc.subject.meshColonic Neoplasms-
dc.subject.meshDNA-
dc.subject.meshDNA Methylation-
dc.subject.meshFemale-
dc.subject.meshGuanine-
dc.subject.meshMice-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshReproducibility of Results-
dc.titleFormation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay.en
dc.typeArticleen
dc.contributor.departmentCRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalToxicology Lettersen
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