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Selected Publications

posted Oct 15, 2009, 7:59 AM by Rachel Aronoff   [ updated Nov 18, 2017, 7:12 AM ]
A collection of citations to research studies on genomic integrity, including measures of DNA damage, links between personal care product ingredients and genetic disease, and other works of note is planned for this space!  

The first paper to cite is one of the classics:
Ames et al PNAS 1975.  Hair Dyes are Mutagenic !!
http://www.pnas.org/content/72/6/2423.full.pdf

The second paper could be the bladder cancer human epidemiology, but instead I will site the Skipper et al 2010 review on arylamines and clear carcinogenesis due to induction of mutations by simple single ring molecules and their metabolites.

The third paper is from Mimi Yu's (of the bladder cancer epidemiology story, 2002) chemist collaborateur, showing that a class 1 carcinogen contaminant, one that could be avoided with further purification, is indeed found in certain hair dye ingredients.  Would you pay more to be a bit safer?  If it's as with bio food - quite possibly, I'd guess!
Turesky et al (2003)
Identification of Aminobiphenyl Derivatives in Commercial Hair Dye
Here's the nitty gritty about this nasty
contaminant
that was found!

- amazing the power of mass spec in chemistry these days
- he did a dog hair study too...  (linked from the genomicintegrity.org blog now, in a post from 3oct13!)



For the Big Launch of AGiR, I add the link to a thesis from S. Africa, which came out in 2008 from R Preston in the lab of FC Eloff, showing human studies using the comet assay after exposures.  They even make an interesting hypothesis (because of their data) that there could be up-regulation of DNA repair activity in hairdressers!
It turns out that they have a 2013 publication now out on this work, which was sent to me!  I will ask if the pdf can be directly linked also from this site, since the publication doesn't seem to come up in NCBI, but there is one of his studies on exposure to gasoline and DNA damage listed there. (keep up the good work!) 


For the upcoming new year, 2014, the idea that genomic integrity is really an ancient target - even for carcinogenesis by infectious microbes! - is highlighted by this paper from R Guidi in the Frisan lab at the Karolinska Institute!  
The genotoxin studied is basically a DNAse (an enzyme that can cut DNA strands), which can lead to malignant transformation!
Their more recent work shows that vesicular transport is required for the genotoxin's delivery and action in studies with the related typhoid toxin, which causes disease because of its DNAse activity (!)    

to note: other bacteria can express factors that also can induce DNA damage, but are unrelated to classic endonuclease (colibactin, for instance), and even the growth of bacteria as infective agents can induce reactive oxygen species and thus induce (indirectly) DNA damage to impact genomic integrity.


For the spring break, 2014 - 101 days into this year for genomic integrity - the recent reference to a review paper summarizing data supporting the idea that RNA acts to make sure integrity of genomic DNA sequences are maintained will be added!  Unfortunately, the full paper is not available freely from Elsevier's Trends in Cell Biology (March issue, 2014).  However, at least the author, Fabrizio d'Adda di Fagagna, who also had a nice review in Nature Reviews Cancer in 2008, doi:10.1038/nrc2440, has confirmed that the long non-coding RNAs from sites of damage are really essential for activation of the DNA damage response, and that the process is indeed alpha-amanitin sensitive (i.e. RNA Polymerase II is transcribing the lncRNAs, which are processed via the same pathways as other microRNAs). 

Already fall, 2014 - here is one reason that people are going to think more about genomic integrity - because prostate cancer risk is also critically dependent on mutations in DNA Damage Response factors, and some of these seem to be regulated by hormone signalling.  Other reviews focus specifically on one part or another of the DNA repair mechanisms, for instance this one from 2013 especially about mismatch repair, but also BRCA mutations (although identified as a breast cancer risk factor) increase risks of prostate cancer (as mentioned in the prezi)...
With prostate cancer as one of the most commonly diagnosed cancers around, it seems it shouldn't be too long before the other penny drops: the further mutations coming up after repair is impaired likely promote metastatic progression...  Maintenance of 'genomic integrity' is crucial!
  

In terms of what we expose ourselves to - maybe overall the worst dangers are due to things out of our control - but to nonetheless try to limit our own exposures when possible seems like a good idea!
Here is a link to the nice exposé about cosmetic ingredients from 2010 by Annie Leonard and the Story of Stuff project to help you think more about this issue.  Do your best!

A week and a month after its publication, a great open access edition of Cell from March 2013 included a nice paper about how location is always essential, even in the nucleus, and how long non coding RNAs are key for the regulation of most things there.  Just think of it, long non coding RNA expression from 75% of the human genome is more cell type specific than that of protein-coding portions of the genome, which comprise only about 2% of the human genome.  These lncRNAs are implicated in disease and increasingly targeted for therapies, and interestingly:

lncRNAs appear to be more structured and stable than mRNA transcripts, which facilitate their detection as free nucleic acids in body fluid such as urine and blood—knowledge already put to good use in clinically approved tests for prostate cancer (Fradet et al., 2004; Shappell, 2008; Tinzl et al., 2004). Aberrant lncRNAs can be knocked down in vivo using oligonucleotide ‘‘drugs’’ (Modarresi et al., 2012; Wheeler et al., 2012), which should spur advance in lncRNA genetics and therapeutics. (Batista and Chang, 2013)

This review is well worth exploring, as are many other papers from that special issue of Cell.
If only someone from their lab would come up with something for the art call!
:)

This next link is to a paper from well-known cancer sequencer Michael Stratton.  In fact there is so much data out there now, what in the C. elegans community would have been called 'evidence for genetic epistatis' is possible with human sequencing data!
 (in this case, it is risks due to a breast cancer associated gene and a checkpoint kinase, functioning in the same pathway of DNA repair that provide this evidence!) 


To start the Fifth Year properly of this public service association:


One conclusion is quoted here regarding the drastic age-related sex differences observed:
'relative lack of mitosis in ageing oocytes compared with spermatogonia, which may enrich for  damage-induced DNMs. The maternal-age-related increase of both C> G  DNMs and NCOGCs in particular genomic regions must be due to some  distinctive property of ageing oocytes.'

More information to be considered in the choice to put off childbearing until later??


small doses with big effects:
It seems like a good time to mention here: many things with certain special biological effects, like hormones or mutagens, can indeed cause big effects in spite of very small doses. 
For instance, research on some of the hormone mimetics, in fact (like BisphenolA, with its two phenol rings, which make it look not only like estradiol, but like something that could slip into nucleic acid structures...) has demonstrated mutagenic effects, even to germ cells, but this remains controversial .
Here is something from the end of the abstract for this second paper, showing just how confusing the state of the matter is: 'In conclusion, the data obtained clearly documents that BPA is not mutagenic but exhibit genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity.'   (!!  this was in Mut. Res. from a group in India, not something in a high profile journal...) 
Still, in spite of such difficulties, whether BPA or its alternatives are at all safe in terms of genes, gene expression and animal development does not seem like a wise 'experiment' for us to be doing on ourselves (without any true controls), imho.  
Nonetheless, the point here is to think about how cells work (and that idea about how surviving with the wrong change can be worse than just being killed off) and the evidence out there for very low dose effects.  This now really seems fairly clear, and is a reason why groups like EWG are targeting this compound.  Here is one review that looks at how well low doses of BPA are reliably leading to effects, at doses up to 4 orders of magnitude lower than ordinarily established 'lowest observed adverse effect levels' established before 2013.  
As a sidenote: the reference list on this review paper (277 articles!), just shows what how far things get taken, still to end up with a single ingredient in the midst of controversy.  
How the FDA or other regulatory agencies can make pursue reasonable research on the 1000s of untested compounds used frequently is a big mystery.  All the more reason for us to do our best and be aware of what can be avoided


As the years pass, more and more 'big data' sets need to be carefully analysed to understand what mutations or other alterations to 'genomic integrity' can actually drive disease and which are simply carried along
Here are just a few of the many papers that have been coming out along that line (jan2016):
one in terms of osteoarthritis development (comparing epigenetic marks in nuclei of cartilage specimens from the same person!);
and 
another 'popular news item' about how a key driver in schizophrenia is related to a classic and complex immunoregulatory region of the genome, that when overactive prunes away too many synapes!  (The journal article appeared in Nature this week!)

and finally, for this update to this page in the AGiR! site, there are still key players that help maintain genomic integrity being discovered, for instance the wuho factor that localises to the replication fork…  
Again, dynamic processes in every cell allow us to live healthy lives, and their failure or poisoning by environmental exposures can prevent this!

For Spring 2016 here are
Two papers on chocolate and potential protection for skin cells from UV…  
The positive result - Williams et al
The negative result - Mogollon et al
Maybe cheek cell assays, rather than their 'quantitative sun burn' methodology can resolve the impasse??


Here are some further links to pages about DNA damage detection, its link to cancer and other chronic diseases, and its repair:


This educational link from Nature has a very nice quote at the end for everyone to keep in mind, even as we worry about deleterious mutations and rearrangements, saying; Mutations in an organism's DNA are a part of life. Our genetic code is exposed to a variety of insults that threaten its integrity. But, a rigorous system of checks and balances is in place through the DNA repair machinery. The errors that slip through the cracks may sometimes be associated with disease, but they are also a source of variation that is acted upon by longer-term processes, such as evolution and natural selection.


This has links about comet assays, from the comet assay interest group, especially launched by the company Trevigen, a company marketing DNA damage detecting assays (like comet assays) and other reagents (PARP assays).
The company Trevigen, which sells many kits and analysis tools for molbio, used to include a list of citations from papers that used their reagents, but apparently that link is now 'broken.'  



This link shows a very nice list of citations on environmental exposures leading to DNA damage with links from the bay area company who recently and very successfully 'crowd-funded' their endeavours. They have a great gimmick about 'fine tuning your DNA' for health, and the first kits set to go out in June 2014.  Foci of DNA damage (double stranded breaks) are detected and quantified in their system based on 53bp1, which regulates p53 and also binds RNA (more below).



This is a link to a special issue of the Journal of Molecular Cell Biology from 2011, focused on genomic instability and cancer.  Of special interest is the artical by Zhaohui Feng et al., on p53 and microRNAs, particularly in light of the work by Fabrizio d'Adda di Fagagna of Milan and others showing roles of small RNAs transcribed from the site damaged, and necessary for detection and repair of DNA damage (probably in association with 53bp1, which has an RNA binding domain.



This link is to a special Nature outlook about how environmental toxicology is gradually becoming more open, in the face of clear environmental exposure leading to cases of cancer (little kids getting lung cancer, for instance).  Simple dose/response relationships are not sufficient to clearly quantify risk, and prevention is always better than attempts at a cure...


Here are Some Selected Links from the Prezi 

Many people say the comet assay is the best way to quantitate DNA damage from various exposures.

(Currently, adding genomic specificity with simultaneous use of fluorescence in situ hybridisation in the context of the comet assay is gaining popularity for higher resolution damage detection…)

This review, already highlighted above, tells about RNA dependence of DNA repair (ncRNAs from site of damage)

 

Two links about direct sequencing of DNA to assess damage/modifications 

 

This tells more about 53bp1, a DNA damage response factor with RNA binding domain and interaction with p53, which regulates the choice between apoptosis and survival. 53bp1 is used as the basis for Exogen's DNA damage test. It may perhaps be a more reliable alternative to another DDR factor, gammaH2AX, but both can be visualized as bright foci at double stranded breaks in cell nuclei after appropriate staining procedures.  (Of note, such double stranded breaks can arise from processes other than repair of DNA damage, like recombination, so the jury is still out about the relevance of such methods to monitor in situ DNA damage events.)


As the Association AGiR! is officially 4 years old as of September 2017, and it was felt everyone should try to start out the 5th year right, a set of tweets were posted in the twitter account (@AGIRgenomes) to help people choose simple ways to protect their cells...

These are reproduced here, additionally with some references for further exploration now included for each point...
10 tips to protect genomic integrity

Tweets to start the fifth year of AGiR! off right!

Tip 1: Use a fruit/veg brush & don't just give your produce a quick rinse! Key to washing off pesticides effectively seems to be friction!

Popular Article:

https://beta.theglobeandmail.com/life/health-and-fitness/health/whats-the-best-way-of-removing- pesticides-from-fruits-and-vegetables/article27178000/

(make sure to copy and paste this link, so no new %# show up, otherwise it fails... watch out in particular for a %20 to appear before the word pesticides in the url - delete that and the article will load.)

Published Study:

http://www.ct.gov/caes/cwp/view.asp?a=2815&q=376676

EWG summary on pesticides in produce:

https://www.ewg.org/foodnews/summary.php#.Wbzcu9Og_F0


Tip 2: Stop smoking or dyeing hair & encourage everyone to do likewise! Cigarettes and hairdyes contain mutagens, like aminophenol, & more.

Popular blog post:

http://blog.lifeextension.com/2012/07/is-your-hair-dye-killing-you.html

Recent hair dye / epidemiology review:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543291/

Occupational exposures:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260452/

The old class I contaminant story:

http://pubs.acs.org/doi/abs/10.1021/tx030029r


Tip 3: Make sure to seek shade and cover up when the sun is at its strongest! The newly revived fashion of parasols is highly encouraged!

Old popular article:

http://www.nytimes.com/1996/11/26/science/sun-is-linked-to-mutations-in-skin.html

Health groups' advice:

https://www.sunsmart.com.au/protect-your-skin/seek-shade

One rule of thumb, if your shadow is shorter than you are tall, stay out of the sun:

http://skincancer.dermis.net/content/e03prevention/e25/index_eng.html

But remember UVB might still be getting to you...

http://www.skincancer.org/prevention/sun-protection/Shade

Study also regarding telomere effects (ageing, more on that below, too):

https://www.ncbi.nlm.nih.gov/pubmed/24691053


Tip 4: Enjoy life and laugh frequently! Relief from stress, through humour, could help reduce cellular levels of DNA damage and slow ageing!

Stress and the molecular pathways that lead to DNA damage:

https://www.nature.com/nature/journal/v477/n7364/full/nature10368.html

Review article:

https://www.hindawi.com/journals/omcl/2011/194586/


Tip 5: Eat more fresh food, rather than processed alternatives! Convenience does not make up for lost antioxidants, key nutrients & taste!

Popular info:

http://www.unidine.com/ccgblogs_processedvsfresh/

There are differences in methods of processing, of course...

https://www.theatlantic.com/health/archive/2015/06/is-fresh-food-better-than-processed-or-frozen/397079/

& nutrition is complicated...

http://www.summertomato.com/processed-food-vs-real-food

Some studies:

https://www.ncbi.nlm.nih.gov/pubmed/?term=healthy+diet+study+ageing


Tip 6: Spice up food to really help protect genomic integrity by increasing antioxidant capacities of cells. Cook with curcumin and ginger.

https://www.ncbi.nlm.nih.gov/pubmed/23378457

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518252/


Tip 7: (re: tips 2x3): Be very wary of following fashion trends! What can be purchased is not necessarily best for you or us all!

This is about many things, like wanting to have a tan, not have any grey hairs, and smoke... but is really not so much about things like this:

http://time.com/3931710/fashion-dangers-skinny-jeans/


Tip 8: Drink water. Sugary soda and alcohol both result in metabolites (reactive oxygen species, aldehydes) that damage cells' molecules.

Popular press:

http://www.health.com/food/sugary-drinks-bad-soda

A review alcohol to aldehyde:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872347/

& cancer risk:

https://pubs.niaaa.nih.gov/publications/arh301/38-47.htm



Tip 9: (re: tip 6): Spices can be protective also via antimicrobial activities, as certain microbial toxins attack DNA& increase cancer risk.

http://www.hi-tm.com/Documents/Spices.html

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-89132005000500007

https://www.ncbi.nlm.nih.gov/pubmed/15180577


Tip 10: Open access to shared information enables true citizen science. Trans-disciplinary and international - together we are better...

https://ecsa.citizen-science.net/working-groups/citizen-science-and-open-science

http://www.hackuarium.ch/

https://groups.google.com/forum/?fromgroups#!forum/diyscience



Tips were put up in Sept.2017

https://twitter.com/AGIRgenomes






Other Links to Follow and Use to find Further Information:




The old BioMednet Central journal specifically devoted to research on DNA damage responses and mechanisms maintaining genome stability.  Apparently inactive now (ca. 2014-), but still providing open access papers about important topics, like, for instance, the genetic basis for the choice between homologous recombination and non-homologous end joining
To note: this open access journal was just beginning at just about the same epoch as the domain, genomicintegrity.org, raising hopes for some 'tipping point' of public awareness about such issues!

However, as of June 2014, this is the notice found on their site!  

Genome Integrity has ceased to be published by BioMed Central as of June 2014. The journal will continue in cooperation with MedKnow publications. Please contact the Editor-in-Chief for information regarding the new publisher and submission process.

BioMed Central will continue to host an archive of all articles previously published in the journal and all articles published inGenome Integrity during its time with BioMed Central will remain fully searchable via the BioMed Central website.

Wonder why?  Some of us remember the early days of BioMedNet, but who knows the policies of BioMed Central these days?  Anyone can ask the editor-in-chief, however...  
(and a note has been already sent to Singapore to ask for more details!)

Perhaps they will continue to publish good work, but the impact factor war and biggies like Elsevier could be problematic.  To follow...



The Environmental Working group database with info about personal care product ingredients.
This lobbying group has started some interesting actions, and also gained apparent enemies (Fox news supporters?).  While it is not clear exactly how much research they actually have going, they have some good gift ideas and are good to check out, also for their 'dirty dozen/generally clean' lists of foods...

They used to have a database also about telephone emissions, but this has been stopped.
Of interest, the blog linked to AGiR! comments further on this issue (21june2014 post)…
Their latest database info push is about food items in general, and they even have a special 'rate your plate' tool to help you make healthy eating choices…

They are a lobbying group and have been criticised in various ways, but their efforts are appreciated, particularly in terms of rating various ingredients and products!  (But some of their critiques put out a book with a title - to paraphrase - 'so there's lead in your lipstick? so what?' and other pro-chem items...  Thus it is hard to say too much without further data.)

In contrast, providing a complementary perspective, AGiR! focuses on dynamic effects of the sum of all these common factors, especially the ones we can choose, on damage and repair in cells, and not only on the fidelity of the genetic code, but that its expression is appropriately controlled.



Here is an amazing source for infographics, fun 'facts' and scientific explorations of everyday chemical compounds.  Thanks to their easy guide to good science, anyone can see how to evaluate research and learn to spot a 'study proving x' that needs to be taken with more than a grain of salt...




The next link is to the key site for scientific citations and info, the National Center for Biotechnology Information (NCBI) 'PubMed' server, where you can search through more than 24 million scientific citations:




For instance, a search as above for 'hair dye and human health' gave 186 hits (Dec. 2014 values), and 204 hits (Feb. 2016 values) including a 2013 epidemiology study from Brazil on maternal use of hair dye and hair straightening products linked to childhood leukemia prevalence, while a search for 'DNA damage and personal care products' only finds 17, some of them showing that certain compounds (like some complex synthetic aldehydes used in the cosmetic industry) are not genotoxic, and others showing clear genotoxic and cytotoxic effects (from benzaldehyde and butyl cyclohexyl phthalate, for example).

Have a look!  You can start with the above, and put in your own search terms…
Treat it like google and see what you find!  

Certain journals are possibly more likely to be more reliable, it should be noted.  Several scandals in the scientific literature have clearly demonstrated that not all papers are equal!  
Also, fyi, an important indication for whether a particular article is valid is whether it is cited by subsequent journal articles! 


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Rachel Aronoff,
Nov 18, 2017, 7:12 AM