O6-Methylguanine methyltransferase activity is increased in rat tissues by ionising radiation |
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| Authors: | Margison GP; Butler J; Hoey Brigid |
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| Institution: | 1Department of Carcinogenesis, Paterson Laboratories, Christie Hospital Withington, Manchester M20 9BX, UK
2Department of Biophysical Chemistry, Paterson Laboratories, Christie Hospital Withington, Manchester M20 9BX, UK |
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| Abstract: | The effect of whole body ionising radiation from a linear acceleratoron rat tissue O6-methylguanine (O6-meG) methyl-transferase (MT)activity has been assessed using an assay which measures thetransfer of 3H-radioactivity from 3H-methylated substrate DNAto protein. The maximal effect occurred 2 days after a 1 kraddose, at which time activity in liver extracts was increased 5-fold in two different rat strains. Activity in lung and kidneywas increased 4- and 2-fold, respectively. Similar degrees ofenhancement were found in these three tissues using an h.p.l.c.method for measuring MT activity. The increase in activity wasreflected in an increased capacity to repair O6-meG producedin liver DNA by administration of 14C]dimethylnitrosamine (DMN):this effect was dose dependent, being detectable after 30 radsand maximal after 600 rads. Incorporation of labelled breakdownproducts of the DMN into adenine in DNA increased as the doseradiation increased suggesting an inhibition of DNA synthesis.The implications of these results for the mechanism of enhancingO6-meG repair are discussed. |
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