Molecule Jenkins

When the tail moment was categorized into tertile values, there was a positive association between increasing risk with higher levels of DNA damage across the tertiles for both the baseline and radiationinduced comets.The comet assay can also be adapted to measure DNA repair.Postexposure decrease of migration indicates that the DNA lesions are repaired.They measured DRC after a fixed time as the percentage of undamaged cells after bleomycin treatment divided by the percentage of undamaged cells in the control population.DRC in lymphocyte subpopulations, from an individual, exhibit similar {|reasch {Endurobol|Amiodarone repair capacities.Furthermore, intraindividual variation in repair capacity in different subpopulations of lymphocytes is significantly smaller than is interindividual variation. There are also published studies showing that reduced repair capacity may aggregate in firstdegree relatives of cancer probands showed that relatives of colorectal cancer patients tended to exhibit higher bleomycininduced bc.Such polymorphisms could explain interindividual differences in DRC. Although the variant alleles are likely to be associated with only modest risk, because they exist at polymorphic frequency, the attributable risks assume substantial relevance.In the following section, we will focus on only two genes from different repair pathways.XPD is one of the seven genetic complementation groups encoding for proteins involved in the NER pathway.The XPD protein has a dual function in NER and in basal transcription.Because many different mutations have been identified in the XPD gene, TFIIH transcriptional activity is probably relatively tolerant to amino acid changes in the XPD protein.It is also possible that mutations could destroy or alter repair function without affecting transcriptional activity.The overall effect of conservative mutations in XPD may be subtle, because they would not alter XPB and XPD helicase activity, and multiple alterations might be needed before any effect was noted.We have published data previously on XPD genotype frequencies in white lung cancer cases and controls. They concluded that cumulative cigarette smoking modifies the association between XPD polymorphisms and lung cancer risk.The next logical step is the challenging task of evaluating the functional relevance of these polymorphisms.There are a variety of factors that modulate the path from genotype to phenotype including proteinprotein interactions, posttranslational modification, gene silencing, epigenetic regulation, and environmental factors.Furthermore, proteins involved in DNA repair pathways are often multifunctional, resulting in a variety of phenotypes.We have evaluated the correlation between some of the DNA repair gene polymorphisms and our functional DNA repair data.Thus, in our dataset, these two XPD polymorphisms were associated consistently with lower DRC in cases with a statistically significant trend and in controls with a nonstatistically significant trend.In other words, the results suggest that these two XPD polymorphisms had a dominant effect on DRC in cases and a smaller effect on DRC in controls.Furthermore, we recently published correlative data on the comet assay and XPD genotypes in the previously cited bladder cancer case control study. These data are consistent with some of the published smallscale studies looking at such genotypephenotype correlations.In addition, subjects with the combined exon AA and exon CC genotype showed a significantly higher levels compared with those with any of the other genotypes, those homozygous for the variant allele had lower DRC.

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