IN-VIVO INDUCTION OF O-6-ALKYLGUANINE-DNA-ALKYLTRANSFERASE IN RESPONSE TO INDIUM-114M

The effect of systemic administration of the radionuclide In-114m on O -6-alkylguanine-DNA-alkyltransferase (ATase) activity has been examine d in rats. In response to 14.8 MBq/kg In-114m injected intraperitoneal ly, hepatic ATase was induced maximally approximately fivefold at 7 da ys after injection, at which time the cumulative radiation dose to the liver was approximately 2 Gy. At 63 days after injection ATase activi ty was still approximately twofold elevated and remained so at 126 day s after injection. By 200 days after injection ATase activity had retu rned to control values. The In-114m 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 d ays 0.03 kBq/g. In response to 4.44 MBq/kg In-114m, 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 day s. There was no ATase induction after 0.44 MBq/kg In-114m up to 7 days after injection; however, at 42 days after injection activity was app roximately twofold higher. These results suggest that induction of hep atic ATase activity by In-114m is dependent upon cumulative radiation dose and dose rate; both must be above minimum threshold values for in duction to occur. The induction of a DNA repair enzyme by radiation ex posure from an internal radionuclide may have important consequences f or risk assessments of occupational, medical and environmental exposur es.