Steps Down the Path to Proving How "Toxins" Cause Disease - Researchers Find Dioxin Impacts on MicroRNA in Fetal Mice
Molecular biologists continue to delve into the specifics of how "toxins" cause harm, thus creating information that someday will end up as part of toxic tort litigation. Working with funds from NIH and the Veterean's Administration, researchers at the University of South Carolina have now published findings of dioxin causing changes to the patterns of microRNA expressed in fetal mice when the mother is exposed to dioxin. The changes appear to matter biologically because microRNA regulate (control) the work of various genes, including genes related to the occurrence of cancers and other diseases. The microRNA changes found here include changes to microRNA tied to cell signaling pathways specifically known to involve diseases such as cancer. The findings thus represent a step down the path of explaining the full biology of why dioxin is "toxic." The pattern of microRNA changes also may - after more work - prove to be a means of fingerprinting a cause of harm in a particular creature.
The paper is: Narendra P. Singh, Udai P. Singh, Hongbing Guan, Prakash Nagarkatti, Mitzi Nagarkatti. Prenatal Exposure to TCDD Triggers Significant Modulation of microRNA Expression Profile in the Thymus That Affects Consequent Gene Expression. PLoS ONE, 2012; 7 (9): e45054 DOI: 10.1371/journal.pone.0045054. ScienceDaily also provides a summary and links.
A press release from the University of South Carolina explains the findings as follows:
For more on microRNA's and their roles, note the following explanations from the article:
"The biological significance of miR generation is evident by their ability to regulate gene expression causing serious effects on various physiological, pathological, and other biological mechanisms and functions. The miRs have been shown to regulate up to 30% of the mammalian genes  suggesting that most cellular pathways are potentially regulated by miRs , , . The effect of miRs can be of various degrees from mild to very strong. The strong effect of miRs is evident from the lethality of knockout mice that lack any of the enzymes responsible for miR production, such as Ago2, Dicer, and Drosha. Some of cellular processes regulated by miRs include apoptosis, cell growth, fat storage, insulin secretion, and cancer initiation and progression , , . miRs may play a significant role in responses to xenobiotic chemicals and their role in causing various health associated problems and ailments. Fukushima et. al. have shown that exposure of rats to liver toxicants such as acetaminophen or carbon tetrachloride caused alteration in the expression of various miRs . In another report, tamoxifen, a potent hepatocarcinogen, was shown to increase the expression of several miRs associated with oncogenes . There are reports demonstrating that cigarette smoking can cause changes in miR expression profile . It has also been shown that mothers smoking cigarettes can exhibit changes in expression levels of miRs related to growth and developmental processes . Similarly, other chemicals, such as bisphenol A, have been shown to cause alteration in miR expression in vitro . There are also reports suggesting that drug-metabolizing enzymes such as CYP family genes are targeted by certain miRs , . These reports suggest that miRs may regulate the toxicity mediated by environmental chemicals.