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aga
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[*] posted on 25-8-2014 at 15:05
Cancer Question


Today i made some Potassium Chromate for a Mohr's titration.

Wiki says it is a 'class 2 carcinogen'.
Sadly wiki does not say what that means.

Has the pathway from K2CrO4 to cancerous cells been explored ?

It seems odd that 'known carcinogens' exist, yet How they do that is still a mystery.

It seems very strange that the whole field of Cancer Research is still quite vague.

Perhaps there is too much money at stake to risk discussion.

[Edited on 25-8-2014 by aga]




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elementcollector1
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[*] posted on 25-8-2014 at 15:12


I don't think it's quite that secretive. A Type II carcinogen is one that *might* be carcinogenetic to humans, with 2A being "probably" and 2B being "possibly". Given the history of hexavalent chromium, this classification is probably just them playing it safe...
Source (World Health Organization): http://monographs.iarc.fr/ENG/Classification/




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aga
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[*] posted on 25-8-2014 at 15:23


So 2B is 'everything else'. OK.

Thanks for the clarification on the classifications.

So of the 113 Group 1 compounds, does anyone know of a study that investigates the pathway from one of those compounds to Cancerous Cells ?




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[*] posted on 25-8-2014 at 20:21


I believe that hexavalent chromium is actually carcinogenic through a pathway involving chromium(III). Chromium(III) is blocked from entering certain parts of a cell which chromium(Vl) can enter by mimicking sulfur(VI), where it is then reduced to chromium(lll) which can then mutate the DNA.
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aga
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[*] posted on 26-8-2014 at 02:05


Thank you gdflp.
I'll look that up.




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Chemosynthesis
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[*] posted on 28-8-2014 at 05:57


Genotoxic substances are hard to characterize due to the stochastic nature of DNA adducts. It does cause strand breakages.
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[*] posted on 28-8-2014 at 06:34


There are biological assays to test the probrability of a chemical to be a carcinogen/mutagen

http://en.wikipedia.org/wiki/Ames_test

otherwise there are studies done on lab mice to determine carcinogenicity, but those typically take time.
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Chemosynthesis
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[*] posted on 28-8-2014 at 09:51


There's also the Comet assay, which has its benefits, but they don't tell the mechanism of genotoxicity/mutagenicity, unfortunately.
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Chemosynthesis
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[*] posted on 10-4-2015 at 12:11


That's really more of a corporate sales site for assays and the like, which caters to people already in the field and familiar with aspects of cancer biology. Not particularly helpful to someone interested in learning some of the disparate mechanisms of oncogenesis.
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aga
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[*] posted on 10-4-2015 at 13:21


Would you happen to have any pointers to other resources then ?



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Chemosynthesis
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[*] posted on 10-4-2015 at 14:23


My advice is pick a cancer or known mechanism/carcinogen of interest and then look into any review papers on the topic. Preferably invited reviews. It would probably be helpful to have a solid background in programmed cell death, oncogenes/tumor suppressors, a few signaling cascades relevant to Bcl-2/caspases, etc.
You can probably get most of what you need in a book like The Biology of Cancer by Weinberg. Note that it's a textbook, since I have recently been carping against books in lieu of peer-reviewed sources.
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aga
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[*] posted on 10-4-2015 at 14:28


Thanks Chemo for the useful pointers.



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Chemosynthesis
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[*] posted on 10-4-2015 at 14:59


No problem. There are other good texts available including Molecular Mechanisms of Cancer by Weber, but Weinberg's second edition is from just last year and supposed to be updated.
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Chemosynthesis
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[*] posted on 25-4-2015 at 05:18


Most organisms don't "catch" cancer because most cancers aren't transmissible. Also, your group is not a cancer research organization... it's a sales company, like the other link above. Not only is that transparently annoying for you to hype product placement without adding to discussion, but it's extremely poorly targeted as this site caters to hobbyist science and not the professional expensive cancer research side of things. I suggest actually meeting scientists, touring labs, and price competing with Fischer reps for some of that business rather than the lazy spam posting route.
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[*] posted on 25-4-2015 at 06:05


Chemo:

His effort may have more to do with link building (Google PageRank improvement) than actual product placement. Either way, it should have no place on this forum.




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[*] posted on 12-7-2015 at 20:05


Quote: Originally posted by Chemosynthesis  
There's also the Comet assay, which has its benefits, but they don't tell the mechanism of genotoxicity/mutagenicity, unfortunately.

It does inform one of the potential mechanisms of genotoxicity. If you observe a longer comet tail in your treated population then double-stranded breaks are most likely the cause of genotoxicty. If you don't see a tail lenght difference under neutral pH but observed a longer tail moment in the treated population under alkaline conditions then single-stranded breaks are the culprit. Also in the alkaline comet assay if you observe a longer tail moment in the control population then interstrand crosslinks might be the cause of genotoxicity (not sure whether you have to incubate your samples with a rare cutter or something of that sort).

[Edited on 13-7-2015 by proxymethoxy]
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[*] posted on 15-7-2015 at 06:27


Some surprising IARC class 1 carcinogens:

- Strong inorganic acid mists including sulfuric acid
- Ethanol and alcoholic beverages
- Formaldehyde (and thus methanol since the aldehyde is a metabolite)
- Wood dust

These are in the same category as benzene, asbestos, smoking tobacco, cadmium, and chromium VI.




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[*] posted on 15-7-2015 at 07:25


Formaldehyde is a known carcinogenic, as it cross-links about any big organic molecule in your body (DNA/RNA/proteins/lipids).

Ethanol is not to surprising either as anything that is irritating is a carcinogenic. Probably the reason for ethanol to be on that list is the huge amount of data that is available on that specific compound.
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[*] posted on 16-7-2015 at 09:30


Ethanol is not carcinogenic per se, its oxidized to acetaldehyde which is a DNA crosslinker.
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[*] posted on 16-7-2015 at 11:47


Oral, œsophageal, laryngeal, and pharyngeal cancers are more common in alcohol users than in non-alcohol
users. Smokers who also drink are at much higher risk. Although the combination of tobacco and alcohol
use significantly increases the risk of developing these cancers, alcohol use alone also increases the risk of
developing them.




F. de Lalande and M. Prud'homme showed that a mixture of boric oxide and sodium chloride is decomposed in a stream of dry air or oxygen at a red heat with the evolution of chlorine.
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[*] posted on 18-7-2015 at 11:13


That is why I think it is save to say that ethanol is a carcinogen on its own without being metabolized to acetaldehyde. This metabolizing happens in the liver which wouldn't explain the higher risk of cancer in the upper digestive track.
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aga
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[*] posted on 18-7-2015 at 15:37


Quote: Originally posted by Tsjerk  
Formaldehyde is a known carcinogenic, as it cross-links about any big organic molecule in your body (DNA/RNA/proteins/lipids).

Could Formaldehyde cross-link even unsaturated fats ?

It may be a carcinogen, but it smells better than S2Cl2 and could make a good factice from oils.




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[*] posted on 18-7-2015 at 16:40


Quote: Originally posted by aga  
Quote: Originally posted by Tsjerk  
Formaldehyde is a known carcinogenic, as it cross-links about any big organic molecule in your body (DNA/RNA/proteins/lipids).

Could Formaldehyde cross-link even unsaturated fats ?

It may be a carcinogen, but it smells better than S2Cl2 and could make a good factice from oils.
\

I'm pretty sure Tsjerk is incorrect about the scope of the cross linking that formaldehyde is capable of. Formaldehyde primarily reacts with the nitrogen atoms of proteins and cross links them. DNA can be cross linked to protein with formaldehyde as in chromatin immunoprecipitation (ChIP) though I'm not sure whether this is dependent on the nitrogenous bases of DNA.

I believe when formaldehyde is used to fix cells or tissue most non-proteinaceous macromolecules are simply trapped in the matrix of cross linked proteins.

Also what is a factice aga?

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[*] posted on 18-7-2015 at 22:56


Quote: Originally posted by Tsjerk  
That is why I think it is save to say that ethanol is a carcinogen on its own without being metabolized to acetaldehyde. This metabolizing happens in the liver which wouldn't explain the higher risk of cancer in the upper digestive track.

I see your logic and I like it. Could you propose a mechanism of ethanol (and not its oxidized metabolites) genotoxicity?
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[*] posted on 18-7-2015 at 23:56


@Proxymethoxy:

I think it must have something to do with the irritating factor of ethanol, so maybe free radicals that damage cells that therefor have to repair themselves and only succeed partially?

About the cross linking: I'm 100% sure formaldehyde also cross links lipids. I don't know whether it can cross link saturated alkyl chains, but than again, the head groups of phospholipids are full of double bonds. I use formaldehyde to fix liposomes before super resolution microscopy, these liposomes consist of E. coli total polar lipids and 1 to 2 molecules of my protein of interest. The protein content is way to low to account for the fixing of the liposomes (200nm), but my protein get nicely trapped after cross linking.
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