An assay has been developed that permits analysis of repair of A/G mismatches to CG base pairs in cell extracts of Salmonella typhimurium LT2. This A/G mismatch repair is independent of ATP, dam methylation, and mutS gene function. The gene product of mutB has been shown to be involved in the dam-independent pathway through the in vitro assay. Moreover, specific DNA-protein complexes and an endonuclease can be detected in S. typhimurium extracts by using DNA fragments containing an A/G mismatch. These activities are not observed with substrates which have a T/G mismatch or no mismatch. The S. typhimurium endonuclease, like the AMG endonuclease found in Escherichia coli (A-L. Lu and D.-Y. Chang, Cell 54:805-812, 1988), makes incisions at the first phosphodiester bond 3' to and the the second phosphodiester bond 5' to the dA of the A/G mismatch. No incision site was detected on the other DNA strand. Extracts prepared from mutB mutants cannot form A/G mismatch-specific DNA-protein complexes and do not contain the A/G endonuclease activity. Thus the A/G mismatch specific binding and nicking activities are probably involved in the A/G mismatch repair pathway. Preliminary analysis of the mutational spectrum of the mutB strain has indicated that this mutator allele causes an increase in CG-to-A-T transversions without affecting the frequencies of other transversion or transition events. In addition, the mutB gene has been mapped to the 64-min region of the S. typhimurium chromosome. Together, this biochemical and genetic evidence suggests that the mutB gene product of S. typhimurium is the homolog of the E. coli micA (and/or mutY) gene product.
IARCT has played a major role in targeted treatment of head and neck cancers due to the increased intratumoral drug concentrations achieved with this approach. It is proposed that superselective IACRT may become primary therapy for external ear canal tumours due to its safety profile. However, the efficacy and benefits of IACRT over conventional surgery and radiotherapy for the treatment of early external auditory canal tumours has not been systematically determined. The objective of this review is to analyse the results from studies involving IACRT, compare them to clinical studies with surgery and radiotherapy as primary treatment modalities and perform a pooled analysis on the relative efficacy of IACRT
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