The mutagenicity of the reaction of DNA with genotoxic carcinogens

TL;DRAbstract

Mechanisms by which carcinogens induce mutations in human cells can be investigated using carcinogen exposed shuttle vector plasmids. In particular, the pSP189 plasmid can be treated with carcinogens in vitro and transfected into human fibroblasts. Following replication, where DNA repair or mutagenesis occurs, recovered plasmids can be screened in indicator bacteria for induced mutations in the supF gene.
\nThe aim of this study was to establish and utilise assays to investigate the mutagenicity of genotoxic agents. Specifically, two model reactive intermediates of the cancer drug tamoxifen, α-acetoxytamoxifen and 4-hydroxytamoxifen quinone methide (4-OHtamQM), along with binary treatments of BPDE with UVB or UVC radiation were assessed for their mutagenic potential in human cells.
\nThe quantitatively minor DNA adduct of tamoxifen formed by 4-OHtamQM is more mutagenic than the major tamoxifen adduct, formed by a-acetoxytamoxifen in Ad293 cells. The majority of mutations in α-a

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