O6-Methylguanine methyltransferase activity is increased in rat tissues by ionising radiation

The effect of whole body ionising radiation from a linear accelerator on rat tissue O6-methylguanine (O6-meG) methyltransferase (MT) activity has been assessed using an assay which measures the transfer of 3H-radioactivity from 3H-methylated substrate DNA to protein. The maximal effect occurred 2 days after a 1 krad dose, at which time activity in liver extracts was increased approximately 5-fold in two different rat strains. Activity in lung and kidney was increased approximately 4- and 2-fold, respectively. Similar degrees of enhancement were found in these three tissues using an h.p.l.c. method for measuring MT activity. The increase in activity was reflected in an increased capacity to repair O6-meG produced in liver DNA by administration of [14C]dimethylnitrosamine (DMN): this effect was dose dependent, being detectable after 30 rads and maximal after 600 rads. Incorporation of labelled breakdown products of the DMN into adenine in DNA increased as the dose radiation increased suggesting an inhibition of DNA synthesis. The implications of these results for the mechanism of enhancing O6-meG repair are discussed.