Abstract
Recent work from my lab has discovered that metabolism generates reactive aldehydes. These reactive molecules are potent at damaging DNA, and the consequences of this are revealed by the combined inactivation of enzymes that detoxify these aldehydes and the Fanconi anemia DNA repair pathway in mice and vertebrate cell lines. I shall discuss this work and recent unpublished work on how natural aldehydes damage blood stem cells. This work has consequences for understanding how metabolism and ethanol exposure can be genotoxic particularly in the vast population of southeast Asians carrying a genetic defect in aldehyde catabolism ( “pink flushers”) and also in the emergence of bone marrow failure and leukaemia in Fanconi Anaemia.
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