I recently wrote a diary in this space on the subject of polychlorinated biphenyls and their effect on killer whale RNA in the Northeastern Pacific. In it, I made reference to polybrominated diphenyl ethers, PBDE's, which are flame retardands that were widely used in a variety of consumer goods, including electronics, and plastic formulations of various types as well as textiles.
An electronic stuff salesman showed up in that diary to inform me that electronics have stopped using PDBE's, but that has had no effect on the concentrations of this class of compounds in the hair of residents in Zhejiang Province in China where the "green" e-waste recycling industry is located. (cf. Sci.Tot.Environ. 397 (2008) 47-56) Similarly in that same province residents show PDBE concentrations in breast milk and in children's blood, unsuprisingly. I, um, wouldn't mention this, except that I know the electronics saleman mostly as a rote anti-nuke of the worst sort and couldn't help myself from pointing out that these people are very, very, very, very, very bad at science, especially when their pocketbooks are involved.
Lest anyone think this is just a Chinese problem, they are also found widely in, um, Norwegian fish, and in fact, lots of other kinds of fish.
A paper in the recent issue of Environmental Science and Technology, a publication of the American Chemical Society, gives an excellent view of the mechanism by which PBDE's attack DNA, and thus give rise to cancers, and other diseases and syndromes related to DNA and RNA. The paper I will discuss from the primary scientific literature is this one:
New Evidence for Toxicity of Polybrominated Diphenyl Ethers: DNA Adduct Formation from Quinone Metabolites,"New Evidence for Toxicity of Polybrominated Diphenyl Ethers:
DNA Adduct Formation from Quinone Metabolites."
Quinones are widely known in nature, by the way, and some are, in fact, essential to life. Coenzyme Q - which is important to cellular respiration - is an example. The structural features of quinones usually involve one or more six membered carbon rings having two double bonds and two doubly bonded oxygens attached to them. They generally form from hydroxyquinones, which have one or more six membered carbon rings and three double bonds internal in the ring as well as two hydroxy atoms attached to them.
Most (but not all) physiologically important quinones (such as coenzyme Q) have the oxygens in the quinone or hydroxyquinone form located with 1,4 geometry, with two carbons (in either direction) between the carbons bonded to oxygens. However some quninones are 1,2 quinones.
Rather than read my laborious description, one can look at pictures, which is the other reason that God invented Google, besides the more popular role of providing anti-nukes from Greenpeace misinformation proving that everyone in Japan was recently killed by Fukushima, although no one was injured at all by, um, falling buildings, collapsed dams or residence in coastal cities.
Anyway. 1,2 quniones (also known as catechols) can be bad for you because their geometry is such that they can react with bases in DNA or RNA, and this sort of thing is thought to be related to certain kinds of estrogen metabolic systems that result in breast, ovarian and related prostate type cancers.
The paper attached does not invoke a quinone mechanism, that is similar is some ways.
Some excerpts from the paper:
Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in many commercial and household products including polyurethane foam, textiles, furniture, and electronics.13 The noncovalent binding of PBDEs in polymers allows the chemicals to enter the environment easily from the product surface during use.4 PBDEs have become contaminants of worldwide concern because of their widespread use, ubiquitous environmental distribution, great bioaccumulation potential, and toxicity.5
I hope no electronic salesmen are offended by this note from the introduction of the paper. Whatever the source, the paper continues:
It is of particular worth to note that the concentrations of PBDEs in human blood, breast milk, and other body tissues have been increasing with a doubling time of approximately 46 years over the last 30 years.6,7...
Now that electronics are "green" again, maybe the rate will slow. I doubt it, but it could happen.
...It is of particular concern to note that metabolic activation of PBDEs could result in hydroquinone and catechol metabolites(diOH-PBDEs with two hydroxyl group at para and ortho positions) that might possess more toxic effects than PBDEs and OH-PBDEs. However, little attention has been paid to the toxicity of hydroquinone and catechol metabolites. Hydroquinone metabolites might undergo peroxidase-catalyzed oxidation to quinones that could create a variety of the hazardous effects in biological systems, including acute cytotoxicity, immunotoxicity, and carcinogenesis.20 The structure change of DNA as a result of covalent binding to carcinogens or their active metabolites was considered as an early critical step in chemical carcinogenesis. If
not being repaired before DNA replication, DNA adducts can cause misrepairing, resulting in mutations and chromosomal alternations.21
Speaking of DNA repair, there was an interesting paper published about DNA and radiation in the famous and important scientific journal Proceedings of the National Academy of Sciences on radiation and DNA that suggests that the so called "linear hypothesis" - on which so many anti-nukes hang their ignorance - about the effects of low level radiation is, um, garbage, but the biological effects of low level radiation is not the topic here.
E-garbage is the topic, even if electronic stuff is, um, "green."
The authors fo the paper followed DNA using ESI-MS-MS which is an extremely sensitive method of analysis that can detect picograms, billionths of a gram, of various compounds and convey not only their concentration, but considerable information about their structural features.
They note in passing that PAH's - which are the products of combustion of dangerous fossil fuels and um, renewable wood - split wood not atoms some people (not me) say - are known to cause cancer via a catecholic/quinone mechanism.
Nobody gives a rat's ass if millions of people die from combustion related cancers each year, which in fact they do every damn year, but a large, if dumb, portion of humanity will scream at the top of their (carbonized) lungs for decades if even one person gets cancer from Fukushima over the next 50 years, not that anyone has (yet).
To take as an example of polycyclic aromatic hydrocarbon (PAH) carcinogenesis, it has been shown that metabolic activation of PAH occurred via a two-step process involving cytochrome P450-mediated formation of hydroquinone metabolites and their further peroxidase-dependent oxidation conversion to PAH-derived quinones. The formed PAH quinones played a critical role in the initiation of cancer by covalent binding to DNA.20 Based on the mechanism for PAH carcinogenesis, it was postulated that PBDE-derived quinones (PBDEQs) might covalently bind to DNA, and the DNA adducts might become biomarkers for the potential of PBDEs to initiate cancer.
Some very cool chemistry follows, with all sorts of cool mechanisms showing how, in fact, PBDE's react with the guanidnyl moiety in DNA. If you're interested, get access to the paper at a good scientific library and at least look at the pictures.
The authors deliberately synthesized a number of guanosinyl/PBDE derivatives and characterized them structurally using NMR as well as mass spectroscopy.
Unsuprisingly they found that indeed found that the purine ring system (which contains two fused heterocyclic rings) and the "guanidnyl" nitrogen external to this system can react with various classes of PBDE's to give two types of ring systems with four fused rings.
What a mess!
Quoth the authors:
After the analysis of dG adducts of PBDEQs was completed, the adduct formation in calf thymus DNA was examined. The generated DNA adducts were not detected in Q-TOF-MS analysis, probably due to the problem of detection limit. UPLC-ESI/S/MS analysis, however, provided good detection on the DNA adducts because much better sensitivity was obtained compared to Q-TOF-MS/MS. The UPLC-ESI-MS/MS analysis of the digestion mixture of DNA treated with PhO-6-BrBQ, 40BrPhO-
6-BrBQ, and 2040BrPhO-6-BrBQ revealed that only one type I adduct was detected and confirmed (Figure S17 in the Supporting Information), probably because the substituted bromine exists at the C-6 position of the quinone ring in these PBDEQs. On the other hand, one type II adduct was observed for 2040BrPhOBQ that does not have bromine on the quinone ring (Figure S17(F) in the Supporting Information). Thus, PBDEQs with a
substituted bromine on the quinone ring is favored for forming a type I adduct, while the absence of bromine on the quinone ring resulted in a type II adduct.
Oh, well then.
Have a great day tomorrow.