PCL477H1-Lecture 6a to post - Lecture 6 overview concept of...

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Lecture 6 overview concept of DNA inter-strand cross-links (ICLs) cross-links produced by agents pathways of cross-link repair relationship to Fanconi Anemia and Hereditary Breast Cancer Susceptibility DNA-protein cross-links caused by agents
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DNA inter-strand cross-link concept inter-strand cross-link: both strands are simultaneously damaged and no undamaged strand is available as a template for repair
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Agents that cause inter-strand cross-links mitomycin C platinum compounds psoralens bifunctional alkylating agents -nitrogen mustards e.g. chlorambucil and mechlorethamine -cyclophosphamide
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Clastogenic effects of inter-strand cross-linking agents
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mitomycin C mitomycin C has been used in the treatment of: adenocarcinomas non-small cell lung carcinoma some leukemias and lymphomas -activated in vivo to an alkylating agent by reductive activation cascade and forms monoadducts and inter- strand or intra-strand cross-links on DNA, preferentially with the N2 position of guanine
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