title: In vivo induction of O6-alkylguanine-DNA-alkyltransferase in response to indium-114m.
abstract: The effect of systemic administration of the radionuclide 114mIn on O6-alkylguanine-DNA-alkyltransferase (ATase) activity has been examined in rats. In response to 14.8 MBq/kg 114mIn injected intraperitoneally, hepatic ATase was induced maximally approximately fivefold at 7 days after injection, at which time the cumulative radiation dose to the liver was approximately 2 Gy. At 63 days after injection ATase activity was still approximately twofold elevated and remained so at 126 days after injection. By 200 days after injection ATase activity had returned to control values. The 114mIn content of the liver increased to a maximum of 28.7 kBq/g 48-72 h after injection, after which it began to decrease such that at 126 days only 0.3 kBq/g remained and at 200 days 0.03 kBq/g. In response to 4.44 MBq/kg 114mIn, hepatic ATase was induced twofold by 7 days after injection, when the liver had received a radiation dose of 0.6 Gy, and was still slightly elevated at 63 days. There was no ATase induction after 0.44 MBq/kg 114mIn up to 7 days after injection; however, at 42 days after injection activity was approximately twofold higher. These results suggest that induction of hepatic ATase activity by 114mIn is dependent upon cumulative radiation dose and dose rate; both must be above minimum threshold values for induction to occur. The induction of a DNA repair enzyme by radiation exposure from an internal radionuclide may have important consequences for risk assessments of occupational, medical and environmental exposures.
authors.affiliation: Cancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: Wilson
authors.forename: K P
authors.initials: KP
authors.lastname: Hoyes
authors.forename: I D
authors.initials: ID
authors.lastname: Morris
authors.forename: H L
authors.initials: HL
authors.lastname: Sharma
authors.forename: J H
authors.initials: JH
authors.lastname: Hendry
authors.forename: G P
authors.initials: GP
authors.lastname: Margison
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction / Q000528:radiation effects; D007205:Indium Radioisotopes; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000528:radiation effects*; D008297:Male; D008780:Methyltransferases / Q000096:biosynthesis* / Q000528:radiation effects; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000201:enzymology / Q000528:radiation effects*; D013737:Testis / Q000201:enzymology / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D007205:Indium Radioisotopes; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase