Arsenic is also known as human carcinogen. Chronic exposure to arsenic-contaminated water in some parts of the world is causing a serious public health hazard around the world.

Chronic arsenic exposure in drinking water leads to the risk of skin, bladder, lung, liver, and kidney cancer. Arsenic also implicate other human diseases such as vascular disorders, peripheral neuropathy, bronchiecstasis, and diabetes, etc. But the exposure of Arsenic, to the infants or to the mothers can lead to the change in gene expressions.

An analysis was carried out by group of researchers, in two phases: (i) Where training population was selected at random and the analyst “blinded” to arsenic exposure level in the test population and (ii) where all arsenic exposure levels of the population was revealed and used to define new training populations.

From the first training population 13 new born subjects were selected at random from 32 new borns. The RNA was extracted from the cord blood of the newborn 1–13, and hybridized to whole human genome arrays. To identify the genes whose expression was associated with prenatal arsenic exposure, an approach was used that combined differential expression testing between the populations, plus a positive or inverse correlation of expression with increasing arsenic exposure. From 13 newborns, first set of expression signature (first gene set) composed of 170 genes were found. These differentiated the unexposed new borns from the arsenic exposed new borns. This prenatal arsenic exposure expression signature of 170 genes was then used to predict prenatal exposure of the remaining population of 19 new borns. The accuracy percent of class prediction was determined after the analysis by revealing the arsenic exposure of the test population to the analyst. Expression of these 170 genes accurately predicted prenatal arsenic exposure in 15 of 19 (79%) newborns.

After testing the arsenic levels of the entire population, it was concluded that the first training population was composed of newborns with a wide range of exposure levels. To assess that a training population based on extreme exposure might yield higher predictive capacity. A second training population having arsenic associated genes was identified using newborns at the extremes of arsenic exposure (i.e, the lowest versus the highest exposures). Six new born comprised of low exposure population and six new born comprised of high exposure population were found. As in the first one, differential expression testing and correlation analysis identified expression signature of 38 genes. These 38 genes were used to predict arsenic exposure in the remaining test population of 20 newborns. This time the accuracy percent was 16 out of 20 (80%) of the newborns.

To yield expression signature of more high predictive capacity, third training population of nine unexposed newborns and 11 exposed newborns were taken. Differential expression testing and correlation analysis identified an expression signature of 11 genes with accuracy of 83% (10 of 12). The power of prediction in this 11 gene is as high as first and second set of genes. Assuming that, these are the key genes involved in the prenatal response of babies to arsenic and represent potential biomarker of arsenic exposures. The potential arsenic biomarker set which was found is composed of transcripts CXL1, DUSP1, EGR-1, IER2, JUNB, MIRN21, OSM, PTGS2, RNF149, SFRS5, and SOC3 genes.

EGR-1 (Early growth response) regulates cell proliferation and is induced by mitogens, it is known to activate cytokines. OSM (oncostatin M) is a member of interlankin-6 (IL-6) family of cytokines and known to control cell cyle progression. Additionaly DUSP1 (Dual specifity phospate 1) is involved in cell cycle regulation and is known to modulate cytokine expression. An inflammation-activated acute phase response is indicated by the presence of the JUNB transcription factor, and IER2 (immediate early response 2) transcripts in the biomarker set.

Concluding that the exposure of the arsenic in different levels to the prenatal state could modulate numerous biological pathways including apoptosis, cell signaling, the inflammatory response, and other stress responses, and ultimately affect health status.

Source: PLOS Genetics,”Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers”

Filed under Arsenic Exposure, Health

You may also like to read

• Exposure To Inorganic Arsenic Causes Prostate Cancer
• Electrician Succumbed To Death Due To Exposure To Lethal Asbestos
• Life Expectancies Are Decreasing In An Alarming Rate Due To Air Pollution
• Maryland Researchers Identify Smallpox Vaccine Faster Than Available Vaccine
• US Air Pollution Standard Not Good For Asthmatic Children

This entry was posted on Sunday, May 18th, 2008 at 8:17 am and is filed under Arsenic Exposure, Health. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.