Does HBV infection induce acute cellular DNA damage?
Gel Technologies Ltd today announced the successful completion of an investment round of $9 million. The funding will be used to accelerate Sol-Gel’s robust pipeline of innovative topical products for the dermatology market. The company’s pipeline includes a new generation of anti-acne kits that target the $1 billion acne therapy market. “Even in the current
Full Post: Gel Technologies raises $9 million
Eukaryotic cells employ multiple strategies of checkpoint signaling and DNA repair mechanisms to monitor and repair damaged DNA.
There are two branches of the checkpoint response pathway, ataxia telangiectasia-mutated (ATM) pathway and ATM-Rad3-related (ATR) pathway. Virus replication presents the host cells with large amounts of exogenous genetic material, including DNA ends and unusual structures. Therefore, infected cells recognize viral replication as a DNA damage stress and elicit DNA damage signal transduction, which ultimately induces apoptosis as part of host immune surveillance. There was no evidence so far that the ATM/ATR kinases or their downstream pathways are triggered by HBV infection.
A research article to be published on October 28, 2008 in the World Journal of Gastroenterology addresses this question. This research group was leaded by Dr Hui Zhong from Beijing Institute of Biotechnology, China.
Using HL7702 hepatocytes with HBV-positive serum as material, they evaluate protein expression levels in HBV infected cells or in non-infected cells; immunofluorescence to show ATR foci ands Chk1 phosphorylation foci formation; flow cytometry to analyze the cell cycle and apoptosis; ultraviolet radiation (UV) and ionizing radiation (IR) treated cells to mimic DNA damage; Trypan blue staining to count the viable cells.
They found that HBV infection induced increased steady state of ATR protein and increased phosphorylation of multiple downstream targets including Chk1, p53 and H2AX. In contrast to ATR and its target, the phosphorylated form of ATM at Ser-1981 and its downstream substrate Chk2 phosphorylation at Thr-68 did not visibly increase upon infection. However, the level of Mre11 and p21 were reduced beginning at 0.5 h after HBV-positive serum addition. Also, HBV infection led to transient cell cycle arrest in the S and the G2 phases without accompanying increased apoptosis. Research on analyzing cell survival change upon radiation followed HBV infection showed that survival of UV treated host cells was greatly increased by HBV infection, owing to the reduced apoptosis. Meanwhile, survival of IR treated host cells was reduced by HBV infection.
Their result indicated that HBV induces cellular DNA damage response dependent on ATR but escapes the consequences of activation of the DNA damage checkpoint by degradation of checkpoint proteins on different levels. The implication of this is that with time, persistent HBV infection may lead to the accumulation of a variety of mutations which would ultimately give rise to HCC.
Scientists at Burnham Institute for Medical Research (Burnham) have demonstrated important new roles for the protein kinase complex Cdc7/Dbf4 or Cdc7/Drf1 (Ddk) in monitoring damage control during DNA replication and reinitiating replication following DNA repair. Since Ddk is often deregulated in human cancers, this new understanding of its role in DNA damage control could help
Full Post: Researchers show mechanisms that regulate DNA damage control and replication
Radiological health expert Daniel Hayes, Ph.D., of the New York City Department of Health and Mental Hygiene suggests that a form of vitamin D could be one of our body’s main protections against damage from low levels of radiation. Writing in the International Journal of Low Radiation, Hayes explains that calcitriol, the active form of
Full Post: Calcitriol - active form of vitamin D - may protect us from radiation
Medicinal plants have been used as traditional remedies for hundreds of years. Among them, S. barbata has been traditionally used in treatment of hepatitis, inflammation, osteomyelitis and gynecological diseases in China. Studies indicate that extracts from S. barbata have growth inhibitory effects on a number of human cancers. Reports are available on the treatment of
Full Post: Researchers look at anti-tumor mechanisms of Scutellaria barbata
An extract from grape seeds forces laboratory leukemia cells to commit cell suicide, according to researchers from the University of Kentucky. They found that within 24 hours, 76 percent of leukemia cells had died after being exposed to the extract. The investigators, who report their findings in the January 1, 2009, issue of Clinical Cancer
Full Post: Extract from grapes kills lab leukemia cells, proving value of natural compounds
An anti-cancer compound found in broccoli and cabbage works by lowering the activity of an enzyme associated with rapidly advancing breast cancer, according to a University of California, Berkeley, study appearing this week in the online early edition of the journal Proceedings of the National Academy of Sciences. The compound, indole-3-carbinol, is already undergoing clinical
Full Post: Broccoli compound, indole-3-carbinol targets key enzyme in late-stage cancer