Genotoxic potential of dental bulk-fill resin composites

OBJECTIVE: To investigate both genotoxicity and hardening of bulk-fill composite materials applied in 4-mm layer thickness and photo-activated for different exposure times. METHODS: Three flowable bulk-fill materials and one conventional flowable composite were filled in molds (height: 4mm) and irradiated for 20 or 30s. The top (0mm) and bottom (4mm) specimen surface were mechanically scraped, and eluates (0.01g composite in 1.5ml RPMI 1640 cell culture media) prepared for each material, surface level and irradiation time. Genotoxicity was assessed in human leukocytes using both the alkaline comet assay and cytokinesis-blocked micronucleus assay, and Knoop hardness (KHN) was measured at the top and bottom specimen surface (n=8). RESULTS: At both irradiation times, none of the bulk-fill composites significantly affected comet assay parameters used in primary DNA damage assessment or induced significant formation of any of the scored chromatin abnormalities (number of micronuclei, nuclear buds, nucleoplasmic bridges), whether eluates were obtained from the top or bottom surface. Furthermore, no decrease in KHN from the top to the bottom surface of the bulk-fill materials was observed. On the other hand, the conventional composite irradiated for 20s showed at 4-mm depth a significant increase in the percentage of DNA that migrated in the tail and a significant increase in the number of nuclear buds, as well as a significant decrease in KHN relative to the top surface. SIGNIFICANCE: Bulk-fill resin composites, in contrast to conventional composite, applied in 4-mm thickness and photo-activated for at least 20s do not induce relevant genotoxic effects or mechanical instability

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The DNA sequence of the human X chromosome

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence