International Commission for Protection Against Environmental Mutagens and Carcinogens. A method for combining and comparing short-term genotoxicity test data: preface. A report from ICPEMC Committee 1. |
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Authors: | D J Brusick J Ashby F J de Serres P H Lohman T Matsushima B E Matter M L Mendelsohn D H Moore S Nesnow M D Waters |
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Institution: | Istituto di Mutagenesi e Differenziamento CNR, Pisa, Italy. |
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Abstract: | The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment. |
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